MultiGen Biotic by Orthoplex White

POSSIBLY EFFECTIVE

• Colic. Oral Bifidobacterium lactis seems to be beneficial for colic. Details: Clinical research in infants with colic shows that taking B. lactis BB-12 (Chr. Hansen, Hoersholm or Bifidolactis Infant, Sofar SpA) drops providing 1 billion colony-forming units (CFUs) daily for 3 or 4 weeks modestly reduces the daily number of crying episodes by about 2.5 when compared with placebo. The proportion of infants with at least a 50% reduction in crying time from baseline was 61% to 80%, compared with 22% to 32% of those taking placebo. Use of B. lactis also resulted in increased sleep time, reduced crying duration, and improved physical and emotional functioning of the caregiver. Stool frequency was decreased in one study, but was not changed in the other (107583,107587).
• Constipation. Oral Bifidobacterium lactis seems to be beneficial for constipation. Details: A meta-analysis of clinical research shows that taking B. lactis increases bowel movement frequency by about 1.5 stools weekly in adults with functional constipation. Specific strains used include LMG P-21384 as 5 billion colony-forming units (CFUs) daily, Bi-07 as 100 million CFUs daily, DN-173 010 as 12.5 billion CFUs daily, and GCL2505 as 10 billion CFUs daily for 2-4 weeks (95342). Another meta-analysis of clinical research in adults with chronic constipation shows that taking B. lactis modestly increases stool frequency when compared with taking placebo. However, there was no effect of taking B. lactis on treatment success, stool consistency, severity of straining or bloating, or gut transit time. Due to the small number of studies, the effect of B. lactis on other symptoms of constipation is unclear from this analysis (110874). A third meta-analysis shows that two specific strains of B. lactis, HN019 and DN-173 010, have medium to large effects on intestinal transit time in mainly healthy adults (110983). The effect of these strains on intestinal transit time in patients with constipation is unclear from this analysis. Clinical research in patients with low defecation frequency also shows that taking the specific B. lactis strain BB-12 (Chr. Hansen A/S) 1-10 billion CFUs daily for 4 weeks increases the odds of improved defecation frequency by about 1.3-fold when compared with placebo (92264). It is possible that any beneficial effect is limited to patients with more severe constipation. One clinical study in patients with functional constipation shows that taking the specific B. lactis strain HN019, 1 or 10 billion CFUs daily for 4 weeks, has no effect on bowel movements when compared with placebo. However, in a post-hoc analysis of patients with three or less weekly stools, this strain of B. lactis modestly increased bowel movements when compared with placebo (98737). Another clinical study in patients with mild chronic constipation shows that taking B. lactis NCC2818 15 billion CFUs daily for 4 weeks does not affect gut transit time, stool output, or symptoms when compared with placebo (102411). B. lactis has also been examined in combination with other ingredients. One small clinical trial using a specific combination product (ID-HWS1000) containing B. lactis IDCC 4301, Bifidobacterium breve IDCC 4401, Lacticaseibacillus casei IDCC 3451, Lactiplantibacillus plantarum IDCC 3501, Lacticaseibacillus rhamnosus IDCC 3201, Lactococcus lactis IDCC 2301, xylooligosaccharide, and dietary fiber as nondigestible maltodextrin, oat fiber, and psyllium husk fiber daily for 4 weeks modestly increases stool frequency and improves symptoms of functional constipation in adults when compared with placebo (107517). Another small clinical trial shows that taking yogurt 180 mL providing B. lactis HN019, L. acidophilus NCFM, and polydextrose (Litesse) daily for 2 weeks modestly improves clinical response and reduces transit time when compared with taking a control yogurt. However, there was no effect on the number of daily bowel movements (90275). Other studies have used B. lactis UABla-12, Bl-04, Bi-07, and/or HN019 in combination with Bifidobacterium bifidum UABb-10, Bifidobacterium longum UABl-14, Lactobacillus acidophilus DDS-1, and fructo-oligosaccharides (FOS) for 4 weeks (110970) or Lactobacillus acidophilus NCFM and Lacticaseibacillus paracasei Lpc-37 for 2 weeks (110979). However, there was a general lack of support for symptom improvement from these studies.
• Irritable bowel syndrome (IBS). Oral Bifidobacterium lactis seems to be beneficial for reducing symptoms of IBS when used alone. Its benefits when used in combination with other probiotics are unclear. Details: Clinical research in adults with IBS shows that taking B. lactis UABla-12 10 billion colony-forming units (CFUs) daily for 6 weeks modestly reduces the severity of abdominal pain when compared with placebo. Also, 28% of patients responded to treatment by having more than a 30% reduction in pain severity, compared with only 16% of those taking placebo. There were also improvements in abdominal distention, duration of pain, and bowel habits (107581). Additional clinical research in children aged 4-16 years shows that taking B. lactis B19 10 billion CFUs daily for 4 weeks reduces bloating, feelings of abdominal fullness, and difficulty with defecation in 25% to 50% of patients with IBS (95350). Some research has also evaluated B. lactis in combination with other probiotics. Clinical research shows that taking a product (Duolac Care) containing B. lactis, Bifidobacterium breve, Lactobacillus acidophilus, Lactiplantibacillus plantarum, Lacticaseibacillus rhamnosus, and Streptococcus thermophilus twice daily for 4 weeks can relieve symptoms in 72% of patients with IBS (95353). Another clinical study in patients with diarrhea-predominant IBS shows that taking a specific multi-species probiotic (NordBiotic, MBM Biotix) containing B. lactis BL040, B. breve BB010, Bifidobacterium longum BL020, Bifidobacterium bifidum BF030, Lacticaseibacillus rhamnosus LR110, Lacticaseibacillus paracasei LPC100, L. acidophilus LA120, Lacticaseibacillus casei LC130, L. plantarum LP140, and Streptococcus thermophilus ST250 as 2.5 billion CFUs total twice daily for 8 weeks improves overall symptom severity, as well as pain severity, pain frequency, and quality of life when compared with placebo. Symptom severity was rated as mild by approximately 60% of those taking the probiotic mixture, compared with 30% of those taking placebo (107516). However, multiple studies show that taking capsules or drinking fermented milk containing a combination of B. lactis BB-12, L. paracasei, and L. acidophilus La510 as 26 billion CFUs total twice daily for 2-6 months does not improve gastrointestinal symptoms in patients with IBS (90236,94696,94697).
• Respiratory tract infections. Most clinical research shows that taking Bifidobacterium lactis alone or in combination with other probiotics may reduce the risk of respiratory infections in otherwise healthy individuals. In patients who are not otherwise healthy, most clinical research shows that taking oral B. lactis has not demonstrated benefit. Details: Clinical research in infants aged 6 to 12 months shows that taking B. lactis HN019 one million colony-forming units (CFUs) per gram of follow-on formula daily for 12 weeks reduces the incidence of confirmed (9.4% vs. 0.0%) and parentally reported (25.0% vs. 9.4%) upper respiratory tract infections when compared to formula without added probiotics. Infants consumed an average of 141 grams of formula daily (110988). Another clinical trial in one month old infants shows that taking B. lactis BB-12 10 billion CFUs daily for an average of about 15 months reduces the proportion of children with respiratory tract infections until age 2 by 13% when compared with taking placebo. The frequency of recurrent respiratory tract infections was not different between groups (95381). In contrast, other clinical research in children attending day care shows that taking B. lactis BB-12 one billion CFUs daily for 3 months does not reduce the duration or incidence of respiratory tract infections (95382). Most research in children also shows that taking B. lactis in combination with other ingredients reduces the risk of respiratory infections. One clinical study shows that children ages 3-5 years who attend day-care centers have significantly fewer influenza-like respiratory symptoms when given milk containing a specific combination of 5 billion CFUs each of B. lactis and Lactobacillus acidophilus (HOWARU Protect, Danisco). Children taking this product seem to have a 45% lower risk of experiencing fever, cough, and rhinorrhea when compared with placebo. The duration of symptoms was also 2 days shorter. These patients were also less likely to use an antibiotic for their symptoms (16847). A clinical study in healthy children aged 3-10 years shows that taking 12.5 billion CFUs daily of a specific combination of B. lactis CUL34 (Lab4), Bifidobacterium bifidum CUL20, and L. acidophilus CUL21 and CUL60, plus vitamin C 50 mg daily reduces the risk of cough by 16% and sore throat by 20% and modestly reduces school absenteeism and antibiotic use when compared with placebo. However, nasal symptoms, fever, and wheezing were not reduced (106943). Another clinical study in children 3-12 years of age with a sick household member shows that taking a combination product (Up4-Junior, UAS Laboratories) containing B. lactis UABLA-12 4 billion CFUs and L. acidophilus DDS-1 1 billion CFUs with fructo-oligosaccharides 50 mg daily for 2 weeks modestly shortens the duration of respiratory infections, but does not reduce the risk of developing an infection, when compared with placebo (98439). In healthy children ages 3-6 years, taking a combination of B. lactis BB-12 and Enterococcus faecium L3 (iNatal Ped, Pharmextracta SpA) 2 billion CFUs each daily for 3 months reduces the incidence of upper respiratory tract infections by 84% compared with children not taking probiotics. The duration of infections was reduced by 50% (110991). The effect of B. lactis on respiratory tract infections has also been examined in adults. In healthy overweight adults or adults with obesity, taking 50 billion CFUs of a specific combination of B. lactis (Lab4P), B. bifidum, L. acidophilus, and Lactiplantibacillus plantarum for 24 weeks reduces the overall likelihood of having upper respiratory tract infection symptoms, such as sneezing, cough, and blocked nose, by approximately 40% when compared with placebo (103439). In college students, clinical research shows that taking B. lactis BB-12 and Lacticaseibacillus rhamnosus LGG one billion CFUs each daily for 12 weeks reduces the duration of upper respiratory tract infection by about 2 days when compared with placebo. Symptom severity was reduced by 34%. There was also a small reduction in the number of missed school days, but not work days (110993). Some research has investigated the effects of B. lactis on respiratory tract infection outcomes in patients who are not otherwise healthy. One clinical trial in children hospitalized with an acute respiratory tract infection shows that taking B. lactis Probio-M8 20 billion CFUs daily from admission until 4 weeks after discharge modestly reduces the duration of nasal, throat, and general aching symptoms when compared with taking placebo. Taking B. lactis also modestly reduced the proportion of patients requiring hospitalization of at least 7 days (110984). Despite these findings, another clinical trial in children and adolescents who are hospitalized shows that taking B. lactis 100 million CFUs daily during a hospital stay does not reduce the incidence or duration of respiratory infections, including common cold, rhinitis, sinusitis, and others, when compared with placebo (92265). Also, in older adults in long-term care, taking a combination of B. lactis BB-12 and Lacticaseibacillus rhamnosus 13-16 billion CFUs daily does not reduce the incidence of upper or lower respiratory infections when compared with placebo over a 12-month period, and increases the use of antibiotics for lower respiratory tract infections by 2.2 days (103425).

POSSIBLY INEFFECTIVE

• Dental caries. Oral Bifidobacterium lactis does not seem to be beneficial for preventing dental caries in young children. Details: Clinical research in infants shows that giving B. lactis BB-12 DSM 15954 (Chr. Hansen A/S) 5 billion colony-forming units (CFUs) daily, starting at age 1-2 months and continuing for an average of 15 months, through a sustained-release pacifier or tablet does not reduce the incidence of dental caries at age 4 when compared with placebo (107588).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Allergic rhinitis (hay fever). Oral Bifidobacterium lactis has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in children aged 6-17 years with allergic rhinitis shows that taking a specific combination product (Inatal ped Pharmaextracta) containing B. lactis BB-12 DSM 15954 and Enterococcus faecium L3 LMG P-27496 2 billion colony-forming units (CFUs) each with oligofructose daily for 3 months prior to a high allergen exposure period the period modestly reduces symptoms of allergic rhinitis and the need for corticosteroids and/or oral antihistamines when compared with baseline (107582). However, other clinical research shows that drinking 250 mL of fermented milk containing B. lactis BB-12 50 billion CFUs, Lacticaseibacillus rhamnosus GG 50 billion CFUs, and Lactobacillus acidophilus La-5 5 billion CFUs from 36 weeks' gestation until 3 months postpartum does not reduce the incidence of allergic rhinitis in the child at 6 years of age when compared with placebo milk (96893).
• Antibiotic-associated diarrhea. Oral Bifidobacterium lactis has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A meta-analysis of 6 clinical trials in hospitalized or outpatient adults shows that taking B. lactis in combination with up to 8 other probiotic strains reduces the risk of antibiotic-associated diarrhea by 30% when compared with taking placebo (107635). However, individual clinical trials have mixed results. Some specific combination products containing B. bifidum have shown benefit for antibiotic-associated diarrhea (AAD). One such product is Ecologic AAD, which contains B. lactis NIZO 3680, Bifidobacterium bifidum NIZO 3804, Enterococcus faecium NIZO 3886, L. acidophilus NIZO 3678 and NIZO 3887, Lacticaseibacillus paracasei NIZO 3672, Lactiplantibacillus plantarum NIZO 3684, Lacticaseibacillus rhamnosus NIZO 3689, and Ligilactobacillus salivarius NIZO 3675. Another evaluated product contains B. lactis BB-12 5.9 billion CFUs daily, L. rhamnosus GG 5.2 billion CFUs, and L. acidophilus La-5 8.3 billion CFUs daily. However, other combinations do not appear to be beneficial. These include B. lactis BB-12 and L. acidophilus LA-5; B. lactis BB-12 and L. rhamnosus; B. lactis, B. bifidum, and L. acidophilus; and B. lactis W51, B. bifidum W23, L. acidophilus W37, L. acidophilus W55, L. paracasei W20, L. plantarum W62, L. rhamnosus W71, and L. salivarius W24 (90239,92255,94692,95348,95405,103425,110969). It is too soon to know which combinations might be most beneficial, if any, for preventing AAD.
• Atopic dermatitis (eczema). It is unclear if oral Bifidobacterium lactis is beneficial for the prevention or treatment of atopic dermatitis. Details: Some research has evaluated B. lactis for TREATING atopic dermatitis. One very small clinical study shows that giving infants a formula containing B. lactis BB-12 (Chr. Hansen A/S) 30-80 billion colony-forming units (CFUs) daily helps reduce the severity of eczema and the markers for allergic responses, including soluble CD4 in serum and eosinophilic protein X in urine when compared with baseline (3458). However, preliminary clinical research shows that giving B. lactis CNCM I-3446 10 billion CFUs to infants as an adjunct to standard topical treatment daily for 3 months does not reduce eczema severity when compared with placebo (90256). B. lactis has also been investigated in combination with other ingredients. In children, taking B. lactis as part of a multi-ingredient formulation for 8 or 12 weeks modestly reduces symptom severity and the need for topical corticosteroids when compared with placebo (107531,110995). In these studies, 1 billion CFUs of a 1:1:1 combination of B. lactis CECT 8145, Lacticaseibacillus casei CECT 9104, and Bifidobacterium longum CECT 7347 daily was used in children ages 4-17 years for 12 weeks (107531) or B. lactis UABLA-12 was taken in combination with Lactobacillus acidophilus DDS-1 for a total of 10 billion CFUs daily along with fructo-oligosaccharide 100 mg (DDS Junior) daily for 8 weeks by children ages 1-3 years (110995). B. lactis-containing probiotics have also been investigated for PREVENTING atopic dermatitis. A meta-analysis of small- to medium-sized studies shows that providing mixed strains of lactobacilli and bifidobacteria to infants during pregnancy and/or in early infancy prevents atopic dermatitis in the child by approximately 40% over the next 0.5-2 years (107503). Although this analysis was not limited to studies examining the effects of B. lactis, seven of the nine studies used B. lactis as part of a combination product. Individual studies included in the analysis have shown that taking a combination of B. lactis, Bifidobacterium bifidum, Ligilactobacillus salivarius, and Lacticaseibacillus paracasei during pregnancy from approximately 35 weeks' gestation until birth, and then giving this combination to the infant after birth until 6 months of age, does not reduce the incidence of eczema at age 2 years, although it does appear to reduce the risk of atopic sensitization by 57% (90234). A secondary analysis of a clinical study included in this analysis in infants aged 8-14 months found that taking a daily mixture of B. lactis and Lacticaseibacillus rhamnosus 1 billion CFUs each daily for 6 months is associated with a lower incidence of eczema when compared with placebo (102286). Also, some clinical research shows that supplementation with 250 mL of fermented milk containing B. lactis BB-12, Lacticaseibacillus rhamnosus GG, and Lactobacillus acidophilus La-5 starting at 36 weeks' gestation and continuing until 3 months postpartum, without supplementation in the infant, reduces the overall occurrence of atopic dermatitis in the child at 2 years of age. At 6 years of age, the effect appears to be inconclusive (96893).
• Bipolar disorder. Oral Bifidobacterium lactis has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in patients with bipolar disorder who were recently hospitalized for a manic episode shows that taking a combination probiotic containing B. lactis BB-12 and Lacticaseibacillus rhamnosus GG 100 million colony-forming units daily for 24 weeks reduces the risk of rehospitalization when compared with placebo. The hazard ratio for the first rehospitalization due to worsening of psychiatric symptoms was 0.37 for the combination probiotic group when compared with placebo. Among patients who were re-hospitalized, taking the combination probiotic reduced the mean duration of rehospitalization by 5.4 days when compared with placebo (96896).
• Cancer. Although there has been interest in using oral Bifidobacterium lactis for cancer prevention or treatment, there is insufficient reliable information about the clinical effects of B. lactis for this condition.
• Canker sores. Oral Bifidobacterium lactis has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One small study shows that taking a combination of B. lactis, Lacticaseibacillus paracasei, Lacticaseibacillus rhamnosus, and Lactobacillus acidophilus reduces pain, but does not affect the number of lesions or healing time, when compared with placebo. Also, another small study shows that using lozenges providing inulin 0.13 gram along with B. lactis and L. acidophilus 1.5 billion colony-forming units each reduces pain, but does not affect ulcer size or healing, when compared with Oracure gel (105146).
• Child development. Oral Bifidobacterium lactis has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: An 11-year follow-up study evaluating B. lactis and Lacticaseibacillus rhamnosus taken daily during pregnancy from 35 weeks' gestation until birth, or six months after birth if breastfeeding, and then giving the same supplement to the infant until 2 years of age, does not affect neurocognitive outcomes such as attention, intelligence, executive function, depression, and anxiety when compared with those taking placebo (102287).
• Clostridioides difficile infection. Oral Bifidobacterium lactis has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A large clinical study in inpatients aged 65 years or older shows that taking a combination of B. lactis, Bifidobacterium bifidium, and Lactobacillus acidophilus 60 billion colony-forming units daily for 21 days does not reduce the incidence of C. difficile diarrhea when compared with placebo (92255). Other combinations also do not appear to be beneficial, including a combination of B. lactis Bi-04, B. lactis Bi-07, Lactobacillus acidophilus, and Lacticaseibacillus paracasei, as well as a combination of B. lactis Bb-12, Lacticaseibacillus rhamnosus GG, and L. acidophilus La-5 (95364).
• Critical illness (trauma). Oral Bifidobacterium lactis has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in multi-trauma patients requiring ventilation shows that taking a combination probiotic containing B. lactis twice daily for 15 days modestly reduces the risk of sepsis, as well as the length of stay in the ICU and hospital, when compared with placebo. The product contained B. lactis BB12 1.75 billion colony-forming units (CFUs) in combination with Lactobacillus acidophilus LA-5 1.75 billion CFUs, Lactiplantibacillus plantarum 500 million CFUs, and Saccharomyces boulardii 1.5 billion CFUs. Half of the dose was given onto the oropharynx and half via a nasogastric tube (107524).
• Dental plaque. It is unclear if Bifidobacterium lactis is beneficial for preventing dental plaque. Details: Preliminary clinical research shows that consuming a yogurt supplemented with B. lactis DN-173010 100 million colony-forming units daily between breakfast and lunch for 4 weeks does not prevent gingivitis or plaque when compared with a placebo yogurt. However, following a non-brushing period of 5 days, both gingivitis and plaque were modestly reduced in individuals consuming the B. lactis-containing yogurt (98502). Clinical research in adolescent boys aged 13-15 years with mild to moderate gingival inflammation shows that taking two lozenges containing B. lactis BB-12 (Chr. Hansen A/S) and Lacticaseibacillus rhamnosus GG (Probiotical SpA) twice daily for 4 weeks does not reduce plaque when compared with placebo. However, there was a benefit on levels of some salivary and plaque pathogenic bacteria. Each lozenge provided B. lactis BB-12 470 million colony-forming units (CFUs) and L. rhamnosus 440 million CFUs (107574). Conversely, a small clinical trial in healthy adults shows that taking four lozenges daily providing a total daily dose of 2 billion CFUs each of B. lactis BB-12 DSM 15954 (Chr. Hansen A/S) and L. rhamnosus GG ATCC 53103 (Probiotical SpA) for 4 weeks modestly reduces plaque when compared with placebo (107572).
• Diabetes. Oral Bifidobacterium lactis has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A meta-analysis of four clinical trials shows that taking probiotics during pregnancy is unlikely to prevent gestational diabetes and increases the risk of pre-eclampsia by 85% when compared with placebo. Although the specific effects of B. lactis are unclear from this analysis, three of the included studies used B. lactis in combination with Lacticaseibacillus rhamnosus (105185). Other clinical research that has found no benefit has used B. lactis BB-12 and L. rhamnosus GG at least 1 billion CFUs daily from 16-20 weeks' gestation until 28 weeks' gestation, or B. lactis 420 DSM 22089 (Dupont Nutrition & Health) and L. rhamnosus HN001 ATCC SD5675 as 10 billion CFUs each daily throughout pregnancy, with or without fish oil (102284,105144). Conversely, one small clinical study in adults with gestational diabetes shows that taking a combination of B. lactis BB-12, Streptococcus thermophilus STY-31, Lactobacillus acidophilus LA-5, and Lactobacillus delbrueckii subsp. bulgaricus LBY-27 for 8 weeks, starting at 24-28 weeks' gestation, modestly reduces fasting blood glucose and improves insulin sensitively when compared with placebo (96892). In children aged 8-17 years with type I diabetes, taking B. lactis Bb12 DSM 15954 and L. rhamnosus GG ATCC 53103 1 billion CFUs daily for 6 months does not reduce insulin requirements or levels of glycated hemoglobin over 12 months when compared with placebo. In addition, C-peptide levels and the maintenance of residual pancreatic beta-cell function were not affected (107518). A small clinical trial in adults with type 2 diabetes shows that taking fermented goat milk 120 grams containing one billion colony-forming units each of B. lactis BB-12 and Lactobacillus acidophilus La-5 daily for 6 weeks modestly reduces levels of glycated hemoglobin and low-density lipoprotein (LDL) cholesterol, but not fasting blood glucose or insulin resistance, when compared with conventional fermented milk containing Streptococcus thermophilus TA-40 (110973).
• Diarrhea. It is unclear if oral Bifidobacterium lactis is beneficial for the treatment or prevention of diarrhea. Details: The European Society for Pediatric Infectious Diseases recommends probiotics in hospitalized children with diarrhea (98469) and the Infectious Disease Society of America (IDSA) recommends probiotics for the outpatient treatment of acute diarrhea (95388). However, B. lactis is not a specific focus of the guidelines and most evidence is low quality. Clinical research shows that B. lactis reduces the duration of acute diarrhea in children by about one day (107636). In older adults in long-term care, clinical research shows that taking a combination of B. lactis BB-12 and Lacticaseibacillus rhamnosus 13-16 billion colony-forming units daily does not reduce the incidence or duration of diarrhea over a 12-month period when compared with placebo (103425).
• Familial hypercholesterolemia. Oral Bifidobacterium lactis has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in children 6-18 years of age with high cholesterol shows that taking a probiotic containing B. lactis MB 2409, Bifidobacterium bifidum MB 109, and Bifidobacterium longum BL04 daily for 12 weeks decreases total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglyceride levels by 2% to 3% and increases HDL cholesterol levels by about 2% when compared with placebo. However, these changes might not be considered clinically significant (98736).
• Generalized anxiety disorder (GAD). Oral Bifidobacterium lactis has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical trial in patients newly diagnosed with GAD shows that taking sertraline 25 mg plus probiotics daily for 8 weeks may modestly reduce some symptoms of anxiety when compared with sertraline alone. However, the reduction in anxiety score was small and change was not consistent between rating scales. Also, the quality of life was not improved. The probiotics provided a total of 18 billion colony-forming units of B. lactis, Bifidobacterium longum, Bifidobacterium bifidum, and Lactobacillus acidophilus (110977).
• Gingivitis. It is unclear if oral Bifidobacterium lactis is beneficial for gingivitis. Details: Preliminary clinical research shows that consuming a yogurt supplemented with B. lactis DN-173010 100 million colony-forming units (CFUs) daily between breakfast and lunch for 4 weeks does not prevent gingivitis or plaque when compared with a placebo yogurt. However, following a non-brushing period of 5 days, both gingivitis and plaque were modestly reduced in individuals consuming the B. lactis-containing yogurt (98502). Another clinical trial following cleaning in patients with gingivitis shows that taking lozenges containing B. lactis HN019 (HOWARU Bifdo LYO 40 DCU-S, Danisco) one billion CFUs twice daily for 8 weeks increases the proportion of patients without generalized gingivitis by almost 50%, and modestly reduces bleeding with probing and gingivitis severity, compared with placebo lozenges. There was no effect on plaque (110992). B. lactis has also been investigated in combination with other ingredients. Clinical research in adolescent boys aged 13-15 years with mild to moderate gingival inflammation shows that taking two lozenges containing B. lactis BB-12 (Chr. Hansen A/S) and Lacticaseibacillus rhamnosus GG (Probiotical SpA) twice daily for 4 weeks modestly reduces gingivitis when compared with placebo. Each lozenge provided B. lactis BB-12 480 million colony-forming units (CFUs) and L. rhamnosus 440 million CFUs (107574). A small clinical trial in healthy adults shows that taking four lozenges daily providing a total daily dose of 2 billion CFUs each of B. lactis BB-12 DSM 15954 (Chr. Hansen A/S) and L. rhamnosus GG ATCC 53103 (Probiotical SpA) for 4 weeks modestly reduces plaque and gingivitis when compared with placebo (107572).
• Helicobacter pylori. It is unclear if oral Bifidobacterium lactis is beneficial for H. pylori; some research suggests that B. lactis may minimize the adverse effects of H. pylori eradication therapy, but not all research agrees. Details: Preliminary clinical research shows that adding B. lactis B94 7 billion colony-forming units (CFUs) daily to sequential H. pylori eradication therapy for 2 weeks results in an eradication rate of 87%, compared with 71% of those taking placebo or using no control along with sequential eradication therapy. Use of B. lactis also reduced treatment non-compliance due to diarrhea during the first week and reduced symptoms such as loss of appetite, nausea, and abdominal pain. In order to have one beneficial outcome, 6.2 patients would need to take B. lactis. There was no overall effect on non-compliance related to diarrhea or to skin rash (107589). Another clinical study shows that taking a specific combination of B. lactis and a lactobacilli species (Ferzym, Specchiasol) 5 billion CFUs daily for one week during standard triple therapy and one week thereafter reduces some treatment-related adverse effects such as taste disturbances and diarrhea, although it does not seem to improve compliance (12763). However, there was no difference in eradication rates or symptom relief in children aged 6-16 years taking B. lactis B94 5 billion CFUs daily plus inulin 900 mg for 14 days along with standard triple therapy (107590). Discrepancies may be related to the population studied or to the B. lactis strain, the other ingredients, or the type of H. pylori treatment used in the available research.
• Hypercholesterolemia. Oral Bifidobacterium lactis has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A meta-analysis of nine small to moderate-sized clinical studies shows that taking a combination of B. lactis and Lactobacillus acidophilus reduces levels of total cholesterol when compared with placebo (107591). Populations in the included clinical trials enrolled patients with hypercholesterolemia, type 2 diabetes, nonalcoholic fatty liver disease (NAFLD), metabolic syndrome, and others. The benefits of B. lactis in patients with hypercholesterolemia are unclear.
• Inflammatory bowel disease (IBD). Oral Bifidobacterium lactis has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small preliminary clinical trial shows that taking 10 billion colony-forming units each of B. lactis BB-12 and Lactobacillus acidophilus LA-5 twice daily for 12 weeks does not increase the proportion of patients with a reduction in weekly bowel frequency of at least 50% when compared with placebo. Also, there was no effect of this combination on stool consistency or abdominal symptoms. However, there were some modest benefits when compared with baseline (110999). This study was small and may have been underpowered to detect differences.
• Malnourishment-related diarrhea. Oral Bifidobacterium lactis has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in children aged 6 months to 4 years of age hospitalized with severe acute malnutrition shows that taking B. lactis BB-12 and Lacticaseibacillus rhamnosus LGG 5 billion colony-forming units each daily during hospitalization and for 8-12 weeks as an outpatient does not affect diarrhea incidence or severity or the number of days with diarrhea during hospitalization. However, the number of days with diarrhea as an outpatient was reduced by 2.2 days (110996).
• Malnutrition. Oral Bifidobacterium lactis has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in children aged 6 months to 4 years of age hospitalized with severe acute malnutrition shows that taking B. lactis BB-12 and Lacticaseibacillus rhamnosus LGG 5 billion colony-forming units each daily during hospitalization and for 8-12 weeks as an outpatient does not affect pneumonia incidence, duration, or severity, weight gain, duration of hospitalization, or other outcomes (110996).
• Metabolic syndrome. It is unclear if oral Bifidobacterium lactis is beneficial for metabolic syndrome. Details: In patients with metabolic syndrome, preliminary clinical research shows that taking fermented milk 80 mL providing B. lactis HN019 27.2 billion colony-forming units daily for 45 days reduces body mass index by approximately 4% and low-density lipoprotein (LDL) cholesterol by approximately 14% when compared with no treatment. There was no effect on waist circumference, glucose control, or other blood lipids (105154).
• Necrotizing enterocolitis (NEC). It is unclear if oral Bifidobacterium lactis is beneficial or safe for NEC prevention. Details: Meta-analyses of clinical research generally show that giving various bifidobacteria species alone does NOT reduce the risk of NEC or all-cause mortality. However, only a few of the studies included in these analyses have used B. lactis (95344,95351,103437,105164). A systematic review of four studies using B. lactis shows that although NEC incidence is reduced by 89% in one study, a significant reduction was not identified in the other studies when compared with placebo (107592). A network meta-analysis of two clinical studies shows that taking a combination probiotic containing B. lactis Bb-12, Bifidobacterium longum subsp. infantis Bb-02, and Streptococcus thermophilus TH-4, reduces the risk of NEC by 71% when compared with control (102437). Despite these findings, guidance among regulatory agencies and clinical organizations varies with respect to the use of probiotics in very low birth weight infants under 1000 grams. The US Food and Drug Administration (FDA) warns that preterm infants given probiotics are at risk of serious infections caused by the bacteria or fungi contained in probiotics due to cases reported in this group of infants (111610). Also, The American Academy of Pediatrics does not support the routine administration of probiotics to preterm infants, particularly those with a birth weight below 1000 grams, due to conflicting data on safety and efficacy and potential for harm in this vulnerable population (111608). The Canadian Paediatric Society, the American Gastroenterological Association, and the European Society for Paediatric Gastroenterology, Hepatology and Nutrition state that probiotic combinations may be of benefit in reducing the incidence of NEC in preterm neonates over 1000 grams. However, B. lactis is not specifically recommended (103003,111609,111611).
• Neonatal jaundice. It is unclear if oral Bifidobacterium lactis is beneficial for neonatal jaundice. Details: Clinical research in newborns with jaundice shows that taking B. lactis CP-9 5 billion colony-forming units twice daily during conventional phototherapy treatment reduces the duration of phototherapy by about 13 hours and modestly improves the decline in serum bilirubin when compared with taking placebo. A sub-analysis shows that this benefit is limited to full-term, and not preterm, newborns (110987).
• Nonalcoholic fatty liver disease (NAFLD). Oral Bifidobacterium lactis has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: In children with NAFLD, clinical research shows that taking a specific combination (Prokid, Gostaresh Milad Pouya Company) containing B. lactis DSMZ 32269 6 billion colony-forming units (CFUs), Lactobacillus acidophilus ATCC B3208 3 billion CFUs, Lacticaseibacillus rhamnosus DSMZ 21690 2 billion CFUs, and Bifidobacterium bifidum ATCC SD6576 2 billion CFUs daily for 12 weeks normalizes liver sonography findings in 53% of children, compared with 17% of those taking placebo. In addition, levels of alanine aminotransferase and aspartate aminotransferase are reduced by 30% and 25%, respectively. There was no effect on body mass index or blood lipids when compared with placebo (105156). However, other research in adults with NAFLD shows that taking probiotic yogurt 100 grams fortified with vitamin D 1000 IU plus B. lactis Bb-12 and L. acidophilus 40 million CFUs daily for 3 months does not improve fasting blood glucose levels, insulin levels, blood pressure, or anthropometric indices when compared with unfortified yogurt (105174).
• Obesity. It is unclear if oral Bifidobacterium lactis is beneficial for weight loss. Details: Clinical research in overweight and obese adults shows that taking B. lactis 420 10 billion colony-forming units (CFUs) daily for 6 months does not reduce body fat or body weight when compared with placebo (95356). However, in individuals with abdominal obesity, clinical research shows that taking B. lactis CECT 8145 (Ba8145) 10 billion CFUs for 3 months modestly decreases body mass index (BMI) when compared with placebo. Also, taking heat-killed B. lactis CECT 8145 (Ba8145) 10 billion CFUs modestly decreases waist circumference when compared with placebo. Sub-group analyses show that these benefits occur only in females, and there was no effect of these products on the visceral or subcutaneous fat areas when compared with placebo (105551). Another clinical trial shows that taking 10 billion colony-forming units each of B. lactis 420 and Lacticaseibacillus rhamnosus HN001 daily, alone and with fish oil providing eicosapentaenoic acid 0.22 grams and docosahexaenoic acid 1.9 grams (Croda Europe Ltd.), during pregnancy and for 6 months postpartum, reduces the odds of overweight at 24 months by approximately 64% or 78%, respectively, when compared with taking placebo (110336). When taken in combination with Lactobacillus acidophilus LA02, B. lactis BS01 2 billion CFUs daily for 6 weeks does not reduce body weight or body fat when compared with placebo in young, healthy individuals, only some of whom were overweight (103438). In contrast to these findings, clinical research shows that taking 50 billion CFUs of a specific combination of B. lactis, Bifidobacterium bifidum, L. acidophilus, and Lactiplantibacillus plantarum (Lab4P) for 24 weeks reduces body weight by an additional 1.3 kg more than placebo (103439). Heat-killed B. lactis has also been investigated in combination with other ingredientd. Clinical research shows that taking enriched seafood sticks 50 grams daily providing heat-inactivated B. lactis CECT 8145 5 billion colony-forming units, inulin 1.7 grams, and eicosapentaenoic acid plus docosahexaenoic acid 370 mg daily for 12 weeks does not reduce body weight, body fat, blood pressure, or most lipid or glycemic indices, when compared to taking conventional seafood sticks. There was a modest decrease in insulin levels in males (110997).
• Oropharyngeal candidiasis. Oral Bifidobacterium lactis has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: In older adults in long-term care, clinical research shows that taking a combination of B. lactis BB-12 and Lacticaseibacillus rhamnosus 13-16 billion colony-forming units daily does not reduce the incidence of oropharyngeal candidiasis when compared with placebo over a 12-month period (103425).
• Otitis media. It is unclear if oral Bifidobacterium lactis is beneficial for preventing otitis media. Details: Clinical research in one month old infants shows that taking B. lactis BB-12 10 billion colony-forming units daily for an average of about 15 months does not reduce the proportion of children with otitis media by two years of age when compared with taking placebo (95381).
• Periodontitis. It is unclear if oral Bifidobacterium lactis is beneficial for periodontitis. Details: In patients with periodontitis, a small clinical trial shows that taking B. lactis HN019 lozenges providing 1 billion colony-forming units twice daily (HOWARU1 Bifido LYO 40 DCU-S, DuPont Danisco Sweeteners Oy) for 30 days after scaling and root planing modestly improves some measures of periodontitis 60 days after treatment completion, including pocket depth and clinical attachment, when compared with using placebo lozenges. In addition, although the risk for disease progression was not improved when compared with placebo, there was a reduction in the need for additional therapy in at least three sites (105157,105158,107622).
• Postoperative bowel function. It is unclear if oral Bifidobacterium lactis is beneficial for improving postoperative bowel function. Details: Clinical research in patients undergoing colorectal polyp resection shows that taking B. lactis MH-02 2 billion colony-forming units daily for 7 days postoperatively does not reduce total postoperative gastrointestinal symptom severity when compared with taking placebo. However, the time to recovery of bowel function was reduced by about 0.7 days and there were modest improvements in defecation difficulty (110985).
• Postpartum depression. Oral Bifidobacterium lactis has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research shows that taking a combination of B. lactis 420 DSM 22,089 and Lacticaseibacillus rhamnosus HN001 ATCC SD5675 (Dupont Nutrition & Health) 10 billion CFUs daily, alone or with fish oil providing eicosapentaenoic acid (EPA) 0.44 grams and docosahexaenoic acid (DHA) 3.8 grams daily, does not reduce symptoms of postpartum depression or anxiety when compared with placebo. Supplements were started in the second trimester of pregnancy and continued until 6 months after delivery (107496).
• Prader-Willi syndrome (PWS). It is unclear if oral Bifidobacterium lactis is beneficial for PWS. Details: A small clinical trial in children with PWS shows that taking B. lactis BPL1 CECT8145 (Archer Daniels Midland Co-Biópolis) 10 billion colony-forming units (CFUs) daily for 12 weeks does not improve fat mass, abdominal adiposity, lipid profile, blood pressure, or glucose control when compared with placebo. However, there was a small improvement in insulin levels and measures of insulin resistance. Also, abdominal adiposity was modestly improved in a sub-group of patients over age 4.5 years, the age at which excessive weight gain typically starts in this population (105149). Other clinical research in children with PWS shows that taking B. lactis BL-11 (Beijing Huayuan Academy of Biotechnology) 30 billion CFUs twice daily for 12 weeks does not affect weight or psychological outcomes, including behavior, communication, and motor skills, when compared with placebo. However, height and overall clinical impression were modestly improved (107585).
• Pregnancy-induced nausea and vomiting. Oral Bifidobacterium lactis has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small preliminary clinical trial shows that taking probiotics during pregnancy reduces the severity and duration of nausea and vomiting by 16% to 54%. There was also a small benefit on stool hardness. A specific probiotic (Probiotics 10, Nature's Bounty) was taken as 2 capsules daily for two back-to-back cycles comprised of six days with probiotics and two days without. Each capsule contained a total of 10 billion colony-forming units (CFUs) of B. lactis Bl-04, Lactiplantibacillus plantarum 299v and DSM 15312, Lactobacillus delbrueckii subsp. bulgaricus Lb-87, Lacticaseibacillus paracasei DSM 13434 and Lpc-37, Ligilactobacillus salivarius Ls-33, Levilactobacillus brevis Lbr-35, Lactobacillus acidophilus La-14, and Lacticaseibacillus casei Lc-11, along with inulin 200 mg (107199).
• Prematurity. It is unclear if oral Bifidobacterium lactis is beneficial for preventing infections in premature infants. Details: A small clinical trial in very low birth weight premature infants shows that taking B. lactis BB-12 two billion colony-forming units per kg six times daily from birth for 6 weeks does not reduce the incidence of nosocomial infections when compared with taking placebo (110994). This study may have been too small to detect differences.
• Psoriasis. Oral Bifidobacterium lactis has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in patients with psoriasis shows that taking a mixture of probiotics for 8 weeks modestly improves overall disease symptoms and feelings of depression when compared with placebo. The percentage of patients achieving at least a 50% or 75% reduction in overall symptom score was 40% and 24%, respectively, compared with 16% and 8% of those taking placebo. The probiotic was taken twice daily and provided a total daily dose of 2.6 billion colony-forming units (CFUs) of B. lactis, Bifidobacterium bifidum, Bifidobacterium longum, and Lactobacillus acidophilus (107498).
• Radiation-induced diarrhea. Oral Bifidobacterium lactis has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in patients with cervical cancer receiving radiotherapy with or without chemotherapy shows that taking a specific product (Biogurt, Fame Pharmaceuticals) containing B. lactis BB-12 and Lactobacillus acidophilus LA-5 1.75 billion lyophilized live colony-forming units in a capsule three times daily throughout radiation treatment reduces the risk of diarrhea by 28% when compared with placebo. Taking probiotics also reduced the use of loperamide when compared with placebo (102285).
• Rheumatoid arthritis (RA). Although there has been interest in using oral Bifidobacterium lactis for RA, there is insufficient reliable information about the clinical effects of B. lactis for this condition.
• Rotaviral diarrhea. It is unclear if oral B. lactis is beneficial for rotaviral diarrhea. Details: Small clinical studies show that giving B. lactis BB-12 alone or along with Streptococcus thermophilus may help reduce the incidence of diarrhea and rotavirus shedding in infants and children up to 36 months old (3169).
• Ulcerative colitis. Oral Bifidobacterium lactis has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical trial shows that taking a specific product (Probio-Tec AB-25) containing B. lactis BB-12 and Lactobacillus acidophilus La-5 is not beneficial for preventing relapse in patients with ulcerative colitis when compared with placebo (95338).
• Urinary tract infections (UTIs). Oral Bifidobacterium lactis has only been evaluated in combination with other ingredients in adults and children; its effect when used alone is unclear. Details: In children aged 4 months to 5 years with a previous UTI, clinical research shows that taking a specific combination (Complete Probiotic Platinum) of B. lactis 750 million colony-forming units (CFUs), Bifidobacterium bifidum 200 million CFUs, Lactobacillus acidophilus 750 million CFUs, and Lacticaseibacillus rhamnosus 50 million CFUs per kg twice daily for 18 months increases the median time to the first incidence of recurrence by approximately 3 months and increases the percentage of children without a UTI during the study period from 83% to 97% (103436). However, in older adults in long-term care, taking a combination of B. lactis BB-12 and L. rhamnosus 13-16 billion CFUs daily does not reduce the incidence of UTI when compared with placebo over a 12-month period (103425).
• Ventilator-associated pneumonia (VAP). Oral Bifidobacterium lactis has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research shows that taking B. lactis BB12 1.75 billion colony-forming units (CFUs), Lactobacillus acidophilus LA-5 1.75 billion CFUs, Lactiplantibacillus plantarum 500 million CFUs, and Saccharomyces boulardii 1.5 billion CFUs twice daily for 15 days reduces the risk of VAP to 12%, compared with 28% of patients taking placebo. Half of the dose was given onto the oropharynx and half via a nasogastric tube (107524). More evidence is needed to rate Bifidobacterium lactis for these uses.

(Read more about BIFIDOBACTERIUM ANIMALIS SUBSP. LACTIS)

POSSIBLY INEFFECTIVE

• Age-related cognitive decline. Oral Bifidobacterium breve does not seem to improve cognition in older adults. Details: A small clinical study in patients over 65 years of age shows that taking a sachet (Morinaga Milk Industry Co., Ltd) containing lyophilized powder of B. breve M-16V and B-3 and Bifidobacterium longum BB536 and M-63 as 12.5 billion colony-forming units each with water daily for 12 weeks does not improve cognition as measured on the Montreal Cognitive Assessment (MoCA) when compared with placebo (102412). While the results of this study may have been limited by the small population size, a larger clinical study in adults ages 50-80 years with subjective memory complaints also shows that using the same product for the same duration does not improve cognition when compared with placebo (102414).
• Sepsis. Oral Bifidobacterium breve does not seem to prevent sepsis in preterm infants. Details: One large, well-designed clinical study in preterm infants shows that taking B. breve BBG-001 up to about 90 billion colony-forming units (CFUs) daily in formula does not reduce the risk of sepsis when compared with placebo (92256). An additional smaller clinical trial also shows that taking B. breve M-16V 3 billion CFUs daily does not reduce the risk of sepsis (111008).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Allergic rhinitis (hay fever). Oral Bifidobacterium breve has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical trial in children ages 4-17 years with allergic rhinitis and intermittent asthma related to Parietaria officinalis pollen shows that taking a combination of B. breve M-16 V one billion colony-forming units (CFUs), Bifidobacterium longum subsp. infantis M-63 one billion CFUs, and B. longum subsp. longum BB536 3 billion CFUs daily for 8 weeks modestly improves symptoms of rhinitis and quality of life when compared to taking placebo. There was no difference in the use of rescue medication (111001).
• Antibiotic-associated diarrhea. Oral Bifidobacterium breve has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in hospitalized patients with antibiotic-associated diarrhea shows that taking a combination of B. breve 50 million colony-forming units (CFUs) and Lacticaseibacillus casei 20 million CFUs three times daily does not reduce the average duration of diarrhea, the frequency of healing, or relapse rates, when compared with taking placebo (111006).
• Asthma. Oral Bifidobacterium breve has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A large clinical trial in children ages 3-14 years with asthma shows that taking a combination of B. breve B632 (DSM 24706) and Ligilactobacillus salivarius LS01 (DSM 22775) one billion colony-forming units (CFUs) each twice daily for 8 weeks and then once daily for 8 weeks modestly reduces the number of asthma exacerbations. The odds of having one or two asthma exacerbation was more than three fold in children taking placebo when compared with children taking probiotics. There was no effect on the duration of exacerbation or use of corticosteroids (111004).
• Atopic dermatitis (eczema). Oral Bifidobacterium breve has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows that taking a total of 10 billion colony-forming units (CFUs) daily of a combination of B. breve M-16V and Bifidobacterium longum subsp. longum BB536 from about 4 weeks before the expected due date until delivery and then giving 5 billion CFUs of this combination daily to the infant for 6 months reduces the odds of developing atopic dermatitis by up to 77% before 18 months of age when compared with no probiotic (111015).
• Atopic disease. Although there has been interest in using oral Bifidobacterium breve for preventing and treating atopic disease, there is insufficient reliable information about the clinical effects of B. breve for this use.
• Celiac disease. Although there has been interest in using oral Bifidobacterium breve for celiac disease, there is insufficient reliable information about the clinical effects of B. breve for this condition.
• Chemotherapy-related infection. Although there has been interest in using oral Bifidobacterium breve for preventing chemotherapy-related infections, there is insufficient reliable information about the clinical effects of B. breve for this purpose.
• Clostridioides difficile infection. Although there has been interest in using oral Bifidobacterium breve for C. difficile infection, there is insufficient reliable information about the clinical effects of B. breve for this condition.
• Cognitive impairment. It is unclear if oral Bifidobacterium breve is beneficial for cognitive impairment. Details: Clinical research in older adults with suspected mild cognitive impairment shows that taking B. breve A1 (MCC1274) 20 billion colony-forming units daily for 16 weeks improves some measures of cognitive function, including immediate and delayed memory, as well as visual spatial ability, by moderate amounts when compared with placebo. However, there was no effect on language or attention (103447). However, taking the same dose for 24 weeks does not improve most measures of cognitive function (111002).
• Colic. It is unclear if oral Bifidobacterium breve is beneficial for colic. Details: Preliminary clinical research in infants with colic shows that adding B. breve CECT7263 200 million colony-forming units (CFUs) daily, or a combination of B. breve with Limosilactobacillus fermentum CECT5716 as 100 million CFUs each daily, to human milk, formula, or water for 28 days reduces the time spent crying per week by approximately 160-200 minutes from baseline. Taking B. breve is at least as effective as taking simethicone 20 mg four times daily (105150). Other clinical research shows that taking B. breve B632 and BR03 100 million CFUs each daily for 3 months modestly reduces daily crying duration when compared with taking placebo (111010). B. breve has also been investigated for colic prevention. Clinical research in infants without colic at baseline shows that adding B. breve CECT7263 10 million CFUs per gram to formula modestly reduces the number of infants crying more than three hours daily when compared with a control formula. At 6 weeks of age, 12% of infants taking formula supplemented with B. breve cried more than 3 hours daily, compared with 29% of those using the control formula. At 4 months of age, frequency of crying more than 3 hours daily was low and not significantly different between groups (105151). However, this study was not specifically designed to examine the effects of B. breve on colic frequency as the infants did not have colic at baseline.
• Constipation. Most early research shows that oral Bifidobacterium breve seems to be beneficial for constipation. Details: Preliminary clinical research in children aged 3-16 years with functional constipation shows that taking a specific B. breve powder (Yakult, Yakult Honsha Co., Ltd.) 1-100 billion colony-forming units (CFUs) daily for 4 weeks increases defecation frequency by about 4 times per week, decreases episodes of fecal incontinence by about 7.5 episodes per week, and improves stool consistency and episodes of abdominal pain (17726). Multi-strain probiotics containing bifidobacteria have also been evaluated for constipation. In children with chronic constipation, preliminary clinical research shows that taking a combination of B. breve M-16 V, Bifidobacterium longum M-63, and B. longum BB536 daily for 8 weeks in addition to polyethylene glycol (PEG), does not improve symptoms or increase the rate of clinical remission when compared with PEG alone (107600). However, one meta-analysis of clinical research in adults with functional constipation shows that taking B. breve DSM 16604 and Lactiplantibacillus plantarum LMG P-21021 as 5 billion CFUs total daily for 30 days improves bowel movement frequency by about 1.5 stools weekly when compared with placebo (95342). Also, a small clinical trial shows that taking a specific combination product (ID-HWS1000) containing Lacticaseibacillus rhamnosus IDCC 3201, L. plantarum IDCC 3501, Lacticaseibacillus casei IDCC 3451, Bifidobacterium animalis subsp. lactis IDCC 4301, Bifidobacterium breve IDCC 4401, Lactococcus lactis IDCC 2301, xylooligosaccharide, and dietary fiber as nondigestible maltodextrin, oat fiber, and psyllium husk fiber modestly increases stool frequency and improves symptoms of functional constipation in adults when compared with placebo (107517).
• Depression. It is unclear if oral Bifidobacterium breve is beneficial for depression. Details: A small clinical trial in patients with major depressive disorder shows that taking B. breve CCFM1025 10 billion colony-forming units (CFUs) daily for 4 weeks modestly improves symptoms of depression when compared with placebo (107602).
• Diabetes. Oral Bifidobacterium breve has only been evaluated in combination with other ingredients for various forms of diabetes; its effect when used alone is unclear. Details: One small clinical study in patients with type 2 diabetes shows that taking a specific combination product (Familact probiotics, ZistTakhmir Co.) containing B. breve and other probiotics daily for 6 weeks does not reduce fasting blood glucose or plasma insulin levels when compared with placebo. This product contains B. breve 30 billion colony-forming units (CFUs), B. longum 7 billion CFUs, Lactobacillus acidophilus 2 billion CFUs, Lacticaseibacillus casei 7 billion CFUs, Lactocaseibacillus rhamnosus 1.5 billion CFUs, Lactobacillus delbrueckii subsp. bulgaricus 200 million CFUs, and Streptococcus thermophilus 1.5 billion CFUs (99790). In adults with gestational diabetes, one clinical study shows that taking a specific product (Visbiome, ExeGi Pharma) containing B. breve and various other probiotics as a total of 112.5 billion CFUs twice daily for 8 weeks does not affect levels of fasting blood glucose or glycated hemoglobin (HbA1c) when compared with placebo. However, there were small improvements in insulin levels and insulin resistance (107549). A combination probiotic containing B. breve has also been evaluated in children 2-12 years of age with new-onset type 1 diabetes. One clinical study shows that taking Visbiome as 112.5 billion CFUs daily for 3 months modestly decreases HbA1c and insulin requirements when compared with placebo. Also, about three times as many children achieved remission, defined as insulin requirements of less than 0.5 U/kg daily and HbA1c levels of less than 7%. However, C-peptide levels and the maintenance of residual pancreatic beta-cell function were not affected when compared with placebo (107497). It is unclear if any benefits are due to B. breve, other probiotics, or the combinations.
• Diarrhea. Oral Bifidobacterium breve has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in children with dysentery being treated with ceftriaxone shows that taking a specific combination probiotic sachet (Kidilact, Zisttakhmir Company) containing B. breve, Lacticaseibacillus casei, Lactobacillus acidophilus, Lacticaseibacillus rhamnosus, Lactobacillus delbrueckii subsp. bulgaricus, Bifidobacterium longum, and Streptococcus thermophilus daily for 5 days modestly reduces the duration of diarrhea, hospitalization, and blood in diarrhea when compared with control (102417). A large clinical trial in infants aged 4-6 months shows that taking an infant formula fermented with B. breve C50 and Streptococcus thermophilus 065 (Calisma) for about 5 months does not affect the incidence or duration of diarrhea episodes when compared with a standard infant formula. However, there was a modest reduction in severity of diarrhea episodes, based on reductions in proportions of infants with dehydration, consultations with medical providers, and need for oral rehydration (111106). This formula did not provide live B. breve.
• Exercise-induced muscle soreness. Oral Bifidobacterium breve has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in resistance-trained males shows that taking B. breve BR03 and Streptococcus thermophilus FP4 as 10 billion colony-forming units total daily for 3 weeks prior to resistance training modestly attenuates range of motion decrements, but does not seem to significantly decrease overall muscle soreness, when compared with placebo (95415).
• Helicobacter pylori. Oral Bifidobacterium breve has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: In adults with H. pylori infection and peptic ulcer disease, adding a combination product containing seven strains of probiotics (Balance by Protexin Co) daily for 14 days to quadruple therapy with omeprazole, bismuth subcitrate, amoxicillin, and clarithromycin does not improve H. pylori eradication or symptoms when compared with quadruple therapy alone. This product provided B. breve, Lacticasebacillus casei, L acticasebacillus rhamnosus, Lactobacillus acidophilus, Lactobacillus delbrueckii subsp. bulgaricus, Bifidobacterium longum, and Streptococcus thermophilus (90291).
• Irritable bowel syndrome (IBS). Oral Bifidobacterium breve has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One clinical study shows that taking a specific combination product (Visbiome, ExeGi Pharma) containing B. breve and other probiotics as 450 billion CFUs daily for 8 weeks decreases bloating in patients with diarrhea-predominant IBS (IBS-D) (11379). However, adding this product as 900 billion CFUs daily to a sham diet or a low-FODMAP diet for 4 weeks does not improve IBS symptoms when compared with placebo (98741). Other clinical research shows that taking a different product (Duolac Care) containing Lactobacillus acidophilus, Lactiplantibacillus plantarum, Lacticaseibacillus rhamnosus, Bifidobacterium breve, Bifidobacterium animalis subsp. lactis, Bifidobacterium longum, and Streptococcus thermophilus twice daily for 4 weeks can relieve symptoms in 72% of patients with IBS (95353). In addition, a clinical study in patients with IBS-D shows that taking a specific combination probiotic (NordBiotic, MBM Biotix) containing B. breve BB010, Lactobacillus acidophilus LA120, Lacticaseibacillus rhamnosus LR110, Lacticaseibacillus paracasei LPC100, Lacticaseibacillus casei LC130, Lactiplantibacillus plantarum LP140, B. longum BL020, Bifidobacterium bifidum BF030, Bifidobacterium animalis subsp. lactis BL040, and Streptococcus thermophilus ST250 as 2.5 billion CFUs total twice daily for 8 weeks improves overall symptom severity, as well as pain severity, pain frequency, and quality of life, when compared with placebo. Symptom severity was rated as mild by approximately 60% of those taking the probiotic mixture, compared with 30% of those taking placebo (107516).
• Metabolic syndrome. Although there has been interest in using oral Bifidobacterium breve for metabolic syndrome, there is insufficient reliable information about the clinical effects of B. breve for this condition.
• Necrotizing enterocolitis (NEC). It is unclear if oral Bifidobacterium breve is beneficial or safe for preventing NEC. Details: One large, well-designed clinical study in preterm infants shows that taking B. breve BBG-001 up to about 90 billion colony-forming units daily in formula does not reduce the risk of NEC when compared with placebo (92256). In a systematic review, four studies show that using B. breve does not reduce the incidence of NEC in most infants. However, in one of the included studies, although there was no effect on the incidence of NEC stage 2 in the total group or in infants born at less than 28 weeks' gestation, the incidence was reduced in infants born at less than 34 weeks' gestation. Also, other preliminary clinical research shows that giving B. breve alone or with Lacticaseibacillus casei reduces the incidence of NEC (107592,107595). Guidance among regulatory agencies and clinical organizations varies with respect to the use of probiotics in very low birth weight infants under 1000 grams. The US Food and Drug Administration (FDA) warns that preterm infants given probiotics are at risk of serious infections caused by the bacteria or fungi contained in probiotics due to cases reported in this group of infants (111610). Also, The American Academy of Pediatrics does not support the routine administration of probiotics to preterm infants, particularly those with a birth weight below 1000 grams, due to conflicting data on safety and efficacy and potential for harm in this vulnerable population (111608). The Canadian Paediatric Society, the American Gastroenterological Association, and the European Society for Paediatric Gastroenterology, Hepatology and Nutrition state that probiotic combinations may be of benefit in reducing the incidence of NEC in preterm neonates over 1000 grams. However, B. breve is not specifically recommended (103003,111609,111611).
• Nonalcoholic fatty liver disease (NAFLD). Oral Bifidobacterium breve has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in patients with NAFLD shows that taking two sachets daily for 3 months of a specific combination product (VSL#3) containing B. breve and other probiotics does not affect body mass index or most glycemic or lipid parameters when compared with taking placebo. However, there was a modest decrease in triglyceride levels and liver enzymes (111009).
• Obesity. It is unclear if oral Bifidobacterium breve is beneficial for obesity. Details: Clinical research in children aged 6-18 years with obesity and insulin resistance shows that adding B. breve BR03 (DSM 16604) and B632 (DSM 24706) 1 billion colony-forming units (CFUs) each daily for 8 weeks to advice on the Mediterranean diet and exercise modestly improves insulin sensitivity when compared with placebo. However, there was no difference between groups in body mass index (BMI) or blood pressure when compared with diet and exercise advice alone (107598). Additional clinical research in overweight, but non-obese, adults based on BMI shows that taking B. breve B-3 5 billion CFUs daily for 12 weeks modestly reduces body fat mass and waist and hip circumference when compared with taking placebo. However, there was no effect on body fat percentage or lipid endpoints (111003).
• Postoperative recovery. Although there has been interest in using oral Bifidobacterium breve for improving postoperative recovery, there is insufficient reliable information about the clinical effects of B. breve for this purpose.
• Pouchitis. Oral Bifidobacterium breve has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research shows that continuous treatment with a specific combination product (Visbiome, ExeGi Pharma) containing B. breve and other probiotics as 6 grams (300-500 billion live bacteria per gram) daily for up to a year seems to maintain remission of pouchitis in 85% of patients (6087,12769).
• Radiation-induced diarrhea. Although there has been interest in using oral Bifidobacterium breve for preventing radiation-induced diarrhea, there is insufficient reliable information about the clinical effects of B. breve for this purpose.
• Respiratory tract infections. Although there has been interest in using oral Bifidobacterium breve for preventing respiratory tract infections, there is insufficient reliable information about the clinical effects of B. breve for this purpose.
• Rotaviral diarrhea. Although there has been interest in using oral Bifidobacterium breve for rotaviral diarrhea, there is insufficient reliable information about the clinical effects of B. breve for this condition.
• Short bowel syndrome. Although there has been interest in using oral Bifidobacterium breve for short bowel syndrome, there is insufficient reliable information about the clinical effects of B. breve for this condition.
• Ulcerative colitis. It is unclear if oral Bifidobacterium breve is beneficial for ulcerative colitis. Details: Some clinical research has evaluated B. breve-containing probiotics for increasing remission rates in patients with ulcerative colitis. The best evidence is for a specific combination product (Visbiome, ExeGi Pharma). Doses of 3 grams (equivalent to 900 billion colony-forming units (CFUs)) once or twice daily has been used in combination with conventional treatment. In children aged 1-16 years, doses of 450-1800 billion CFUs for up to one year have been used (3261,14370,14371,16841,95337). A meta-analysis of clinical research shows that taking this probiotic can increase remission rates by about 1.7-fold when compared with placebo in adults and children with active ulcerative colitis (95337). There is also evidence that it is beneficial for improving remission rates in patients who do not adequately respond to conventional treatment (14371). Additionally, some preliminary clinical research shows that this specific product, taken as an adjunct to standard maintenance therapy, might help prevent relapse (3261,16841). Other preliminary clinical research shows that taking Visbiome or a fermented milk (Yakult, Yakult Honsha Co., Ltd.) containing B. breve, Bifidobacterium bifidum, and Lactobacillus acidophilus as an adjunct to standard maintenance therapy might help prevent relapse in ulcerative colitis patients (3261,12775,14338,16841). However, other research shows that taking B. breve Yakult is not beneficial for preventing ulcerative colitis relapse (98740). More evidence is needed to rate Bifidobacterium breve for these uses.

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INSUFFICIENT RELIABLE EVIDENCE to RATE

• Abdominal pain. It is unclear if oral Bifidobacterium longum is beneficial for abdominal pain or discomfort. Details: Clinical research in adults with abdominal pain, discomfort, and bloating shows that taking B. longum 35624 (Align) one billion colony-forming units daily for 4 weeks does not reduce symptom severity or the frequency of pain and discomfort when compared with placebo. However, there was a 72% increased odds of having at least one day free of abdominal bloating or distension. Individuals in this study had not been seeing a physician but had symptoms at least twice a week for 3 months (111858).
• Acute radiation syndrome. It is unclear if oral Bifidobacterium longum is beneficial for acute radiation syndrome. Details: A small clinical study shows that antibiotic-resistant B. longum can help improve short-term survival in the treatment of radiation sickness. In combination with prophylactic antibiotics, B. longum appears to inhibit colonization and overgrowth of intestinal opportunistic pathogens, preventing post-irradiation sepsis. This study used B. longum 10 billion colony-forming units daily in 10 mL of milk for 30 days, starting approximately 10 days after irradiation (3457).
• Age-related cognitive decline. Oral Bifidobacterium longum has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in patients over 65 years of age shows that taking a sachet (Morinaga Milk Industry Co., Ltd) containing lyophilized powder of B. longum BB536 and M-63, along with B. breve M-16V and B-3 as 12.5 billion colony-forming units (CFUs) each with water daily for 12 weeks does not improve cognition as measured on the Montreal Cognitive Assessment (MoCA) when compared with placebo (102412). While the results of this study may have been limited by the small population size, a larger clinical study in adults ages 50-80 years with subjective memory complaints also shows that using the same product for the same duration does not improve cognition when compared with placebo (102414). Additional clinical research in healthy adults over 65 years shows that taking a total of one billion CFUs of B. longum BORI and Bifidobacterium bifidum BGN4 daily for 12 weeks modestly improves mental flexibility when compared with placebo. However, there were no benefits on cognitive function, including language, memory, or attention (110968).
• Allergic rhinitis (hay fever). Oral Bifidobacterium longum has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in patients with seasonal allergies shows that taking B. longum MM-2 0.15 billion colony-forming units CFUs), Bifidobacterium bifidum G9-1 0.15 billion CFUs, and Lactobacillus gasseri KS-13 1.2 billion CFUs twice daily for 8 weeks during allergy season modestly improves quality of life, specifically nasal symptoms, when compared with taking placebo. However, eye symptoms were not improved (110972). Also, a small clinical trial in children ages 4-17 years with allergic rhinitis and intermittent asthma related to Parietaria officinalis pollen shows that taking a combination of B. longum BB536 3 billion CFUs, B. longum M-63 1 billion CFUs, and Bifidobacterium breve M-16 V 1 billion CFUs, daily for 8 weeks modestly improves symptoms of rhinitis and quality of life when compared to taking placebo. There was no difference in the use of rescue medication (111001).
• Antibiotic-associated diarrhea. It is unclear if oral Bifidobacterium longum is beneficial for preventing antibiotic-associated diarrhea (AAD); the available research is conflicting. Details: One preliminary clinical study shows that taking B. longum can reduce stool frequency, abdominal discomfort, and stool clostridial spore count when used in patients concurrently taking erythromycin (1233). However, other research shows that taking B. longum with clindamycin does not significantly reduce diarrhea (14334). A small clinical trial in children aged 5 months to 16 years shows that taking a combination of B. longum PL03, Lacticaseibacillus rhamnosus KL53A, and Lactiplantibacillus plantarum PL02 twice daily during antibiotic treatment does not reduce the rate of AAD when compared with placebo. However, there was a modest reduction in the number of stools each day (107553).
• Asthma. It is unclear if oral Bifidobacterium longum is beneficial for asthma. Details: Clinical research in patients with asthma shows that taking B. longum 35624 (Alimentary Health Ltd) one billion colony-forming units twice daily for 4 weeks does not reduce asthma severity or inhaler use or improve pulmonary function when compared with taking placebo. However, in a small sub-set of patients with uncontrolled symptoms, well-controlled asthma occurred in 93% of patients taking B. longum compared with 36% of those taking placebo. This benefit was maintained for an additional 4 weeks in 57% of patients. Some measures of pulmonary function were improved (111856).
• Athletic performance. It is unclear if oral Bifidobacterium longum is beneficial for athletic performance. Details: In athletes, preliminary clinical research shows that taking B. longum OLP-01 15 billion colony-forming units in three divided doses daily for 5 weeks with training and de-training does not affect the distance run in 12 minutes when compared with placebo (103446).
• Atopic dermatitis (eczema). Oral Bifidobacterium longum has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Research evaluating B. longum-containing probiotics for preventing atopic dermatitis has been mixed. One clinical study shows that taking a combination of B. longum plus Lacticaseibacillus rhamnosus or Lacticaseibacillus paracasei, beginning about 2 months before expected delivery and continuing through breastfeeding until the infant is 2 months old, reduces the risk of eczema in the infant (90285). Preliminary clinical research also shows that taking a total of 10 billion colony-forming units (CFUs) daily of a combination of B. longum BB536 and Bifidobacterium breve M-16V from about 4 weeks before the expected due date until delivery and then giving 5 billion CFUs of this combination daily to the infant for 6 months reduces the odds of developing atopic dermatitis by up to 77% before 18 months of age when compared with no probiotic (111015). In addition, in children ages 4-17 years, taking 1 billion CFUs of a 1:1:1 combination of B. longum CECT 7347, Lacticaseibacillus casei CECT 9104, and Bifidobacterium animalis subsp. lactis CECT 8145 for 12 weeks modestly reduces symptom severity and the need for topical corticosteroids when compared with placebo (107531). However, in infants with a family history of allergic disease, giving human milk containing B. longum BL999 10 million CFUs and L. rhamnosus 20 million CFUs daily for the first 6 months of life does not seem to reduce the incidence of eczema or atopic sensitization (35396).
• Bronchopulmonary dysplasia. Oral Bifidobacterium longum has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One large observational study in premature infants suggests that taking B. longum 1-1.5 billion colony-forming units with L. acidophilus during the first month of life for the prevention of necrotizing enterocolitis is not associated with a reduced risk of bronchopulmonary dysplasia. The infants in this study were born between 22-29 weeks gestation and had a birthweight of less than 1500 grams (111771).
• Cancer. Although there has been interest in using oral Bifidobacterium longum for cancer prevention or treatment, there is insufficient reliable information about the clinical effects of B. longum for this condition.
• Celiac disease. It is unclear if oral Bifidobacterium longum is beneficial for celiac disease. Details: Preliminary clinical research in children aged 2-17 years with celiac disease shows that taking B. longum CECT 7347 1 billion colony-forming units (CFUs) daily along with a gluten-free diet for 3 months does not improve gastrointestinal symptoms, including diarrhea, constipation, abdominal pain, or vomiting, when compared with placebo (92266). Also, a small clinical trial in adults with persistent symptoms of celiac disease while following a gluten-free diet shows that taking B. longum NLS-SS (Natren Life Start 2, Natren Inc., USA) 4 billion CFUs three times daily for 3 weeks does not reduce symptoms when compared with taking placebo. However, there was a modest benefit in patients with the greatest initial clinical burden (111857). This study might have been too small to detect differences between groups.
• Chemotherapy-related infection. Oral Bifidobacterium longum has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in patients with leukemia receiving chemotherapy shows that taking B. longum in combination with Lactobacillus acidophilus (Morinaga Bifidus), with or without Enterococcus faecalis (Levenin), does not reduce the risk of Candida infection when compared to control (35434).
• Clostridioides difficile infection. Although there has been interest in using oral Bifidobacterium longum for C. difficile infection, there is insufficient reliable information about the clinical effects of B. longum for this condition.
• Cognitive function. It is unclear if oral Bifidobacterium longum is beneficial for improving cognitive function. Details: A small clinical trial in healthy adults ages 60-75 years without cognitive impairment shows that taking B. longum BB68S 50 billion colony-forming units (CFUs) daily for 8 weeks modestly improves cognitive function, including immediate and delayed memory, visuospatial/constructional memory, and attention, when compared with taking placebo. There was no effect on language or some other measures (111776). A small clinical trial in healthy adults shows that taking a product containing a combination of B. longum R0175 70 million CFUs, Lactobacillus helveticus R0052 2 billion CFUs, and Lactiplantibacillus plantarum R1012 800 million CFUs (Puraflor, GSK Consumer Healthcare, Milano, Italy) daily for 4 weeks does not affect cognitive performance during acute stress when compared with placebo. The probiotics were provided in combination with inulin 500 mg, potassium 50 mg, magnesium 45 mg, glutathione 20 mg, lactoferrin 10 mg, and zinc 9 mg (110923). The effects of B. longum alone are not clear from this study. Also, a larger clinical trial is needed to confirm these results.
• Colic. Although there has been interest in using oral B. longum for colic, there is insufficient reliable information about the clinical effects of B. longum for this condition.
• Common cold. Oral Bifidobacterium longum has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in healthy adults shows that taking B. longum, in combination with other probiotics and vitamins/minerals, daily for at least 3 months reduces the duration of common cold episodes by approximately 2 days when compared with taking a placebo providing only the vitamins/minerals. However, there was no difference in the number of common cold episodes. The probiotic supplement provided B. longum SP 07/3 5 million colony-forming units (CFUs), Bifidobacterium bifidum MF 20/5 5 million CFUs, and Lactobacillus gasseri PA 16/8 40 million CFUs (Tribion Harmonis) daily (110978).
• Constipation. It is unclear if oral Bifidobacterium longum is beneficial for constipation. Details: B. longum BB536 in doses of 2-20 billion colony-forming units (CFUs) has been evaluated for constipation in adults, but results are conflicting and modest at best (35413,35424). Multi-strain probiotics containing B. longum have also been evaluated. Clinical research in adults with chronic constipation shows that taking a multi-strain probiotic (Hexbio) containing B. longum, Bifidobacterium bifidum, Lactobacillus acidophilus, Lacticaseibacillus casei, and Lactobacillus delbrueckii subsp. lactis 30 billion CFUs twice daily for 7 days increases the number of weekly bowel movements by about 2 when compared with placebo (90266). However, another study shows that taking B. bifidum UABb-10 300 million CFUs daily for 4 weeks in combination with Bifidobacterium longum UABl-14 300 million CFUs, Bifidobacterium animalis subsp. lactis UABla-12 7.8 billion CFUs, Lactobacillus acidophilus DDS-1 6.6 billion CFUs, and fructo-oligosaccharides (FOS) 7 mg does not improve symptoms of constipation when compared with a placebo providing FOS (110970). Also, in children with chronic constipation, preliminary clinical research shows that taking a combination of B. longum M-63, B. longum BB536, and B. breve M-16 V daily for 8 weeks in addition to polyethylene glycol (PEG) does not improve symptoms or increase the rate of clinical remission when compared with PEG alone (107600). B. longum has also been investigated for constipation prevention in infants. Clinical research in healthy term infants less than 3 months of age shows that consuming infant formula without B. longum for 12 weeks results in a 5.2-fold increased odds of having constipation when compared with consuming a formula supplemented with B. longum CECT7210 10 million CFUs per gram (111825).
• Coronavirus disease 2019 (COVID-19). Oral Bifidobacterium longum has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small, retrospective study in patients with severe COVID-19 symptoms shows that taking a combination of probiotics in three divided doses daily modestly reduces the duration of diarrhea when compared to standard treatments alone. The probiotic treatment consisted of B. longum 60 million colony-forming units (CFUs), Streptococcus thermophilus 6 million CFUs, and Lactobacillus delbrueckii subsp. bulgaricus 6 million CFUs, given in three divided doses daily (107200).
• Depression. Oral Bifidobacterium longum has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One small clinical trial in patients with mild to moderate symptoms of major depressive disorder shows that taking a total of 10 billion colony-forming units (CFUs) of B. longum and Lactobacillus helveticus daily modestly improves symptoms of depression when compared with placebo, but not when compared with the prebiotic galactooligosaccharide. All patients had been taking antidepressants for at least 3 months (102506). Also, preliminary clinical research in treatment-naïve patients with moderate depression shows that taking 0.3 billion CFUs of B. longum in combination with 2.7 billion CFUs of L. helveticus daily modestly improves symptoms of depression and sleep quality when compared with baseline (105129). However, a larger clinical trial in untreated patients with depression shows that taking a total of 3 billion CFUs of B. longum and L. helveticus does not improve symptoms of depression when compared with placebo. The majority of these patients had a history of prior antidepressant usage (110922). All studies used B. longum R0175 and L. helveticus R0052 (Lallemand Health Solutions Inc.) daily for 8 weeks.
• Diabetes. Oral Bifidobacterium longum has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One small clinical study in patients with type 2 diabetes shows that taking a specific combination product (Familact probiotics, ZistTakhmir Co.) containing B. longum and other probiotic bacteria daily for 6 weeks does not reduce fasting blood glucose or plasma insulin levels when compared with placebo. This product contains B. longum 7 billion colony-forming units (CFUs), Bifidobacterium breve 30 billion CFUs, Lactobacillus acidophilus 2 billion CFUs, Lacticaseibacillus casei 7 billion CFUs, Lactocaseibacillus rhamnosus 1.5 billion CFUs, Lactobacillus delbrueckii subsp. bulgaricus 200 million CFUs, and Streptococcus thermophilus 1.5 billion CFUs (99790). Also, a large clinical trial shows that taking B. longum sp54 cs at least 1.5 billion CFUs daily, L. acidophilus LA1 at least 7.5 billion CFUs daily, and Bifidobacterium bifidum sp9 cs at least 6 billion CFUs daily from 14-24 weeks' gestation does not reduce the incidence of gestational diabetes when compared with placebo (107520).
• Diarrhea. It is unclear if oral Bifidobacterium longum is beneficial for diarrhea treatment or prevention. Details: Clinical research in healthy term infants less than 3 months of age shows that consuming infant formula supplemented with B. longum CECT7210 for 12 weeks does not reduce the overall number of diarrhea episodes or the proportion of infants with a diarrhea episode when compared with consuming control infant formula. The probiotic formula provided 10 million colony-forming units (CFUs) per gram (111825). The number of episodes of diarrhea may have been too small to detect differences between groups. B. longum has also been investigated for diarrhea treatment. A small clinical study in children with dysentery being treated with ceftriaxone shows that taking a specific combination probiotic sachet (Kidilact, Zisttakhmir Company) containing B. longum, B. breve, Lacticaseibacillus casei, Lactobacillus acidophilus, Lacticaseibacillus rhamnosus, Lactobacillus delbrueckii subsp. bulgaricus, and Streptococcus thermophilus daily for 5 days modestly reduces the duration of diarrhea, hospitalization, and blood in diarrhea when compared with control (102417). In adults with acute diarrhea, clinical research shows that taking one capsule providing at least 20 million CFUs each of B. longum and Lactobacillus gasseri (Omniflora) three times daily for up to 6 days is as effective as taking Enterococcus faecium SF 68 75 million CFUs three times daily, used as an active comparator, for reducing the duration of diarrhea. However, complete recovery occurred in a modestly greater proportion of patients. All patients also received oral rehydration solution (111854).
• Familial hypercholesterolemia. Oral Bifidobacterium longum has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in children 6-18 years of age with high cholesterol shows that taking a probiotic containing B. longum BL04, Bifidobacterium animalis subsp. lactis MB 2409, and Bifidobacterium bifidum MB 109 daily for 12 weeks reduces total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglyceride levels by 2% to 3% and increases HDL cholesterol levels by about 2% when compared with placebo. However, these changes might not be considered clinically significant (98736).
• Generalized anxiety disorder (GAD). Oral Bifidobacterium longum has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical trial in patients newly diagnosed with GAD shows that taking sertraline 25 mg plus probiotics daily for 8 weeks may modestly reduce some symptoms of anxiety when compared with sertraline alone. However, the reduction in anxiety score was small and change was not consistent between rating scales. Also, the quality of life was not improved. The probiotics provided a total of 18 billion colony-forming units of B. longum, Bifidobacterium bifidum, Bifidobacterium animalis subsp. lactis, and Lactobacillus acidophilus (110977).
• Hepatic encephalopathy. Oral Bifidobacterium longum has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in patients with hepatic encephalopathy shows that taking an unspecified amount of B. longum W11 in combination with fructo-oligosaccharides (Zirfos) 2.5 grams daily for 90 days modestly reduces serum ammonia levels and improves performance on various neuropsychological tests measuring abstract reasoning, memory, motor speed, language, etc., when compared with taking a placebo consisting of B vitamins (111847).
• Helicobacter pylori. Oral Bifidobacterium longum has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A meta-analysis of clinical research in adults shows that taking combination products containing both lactobacilli and bifidobacteria in conjunction with standard therapy increases the odds of H. pylori eradication by approximately 2-fold when compared with standard therapy alone. These combinations also reduce the odds of disease-related side effects by approximately 70% when compared with standard therapy alone. Six of the ten studies in the meta-analysis included B. longum, with two specifying the inclusion of two B. longum subspecies (90601). However, one clinical study has evaluated a combination product containing seven strains of probiotics in adults with H. pylori infection and peptic ulcer disease. In this study, adding this specific probiotic (Balance by Protexin Co) daily for 14 days to quadruple therapy with omeprazole, bismuth subcitrate, amoxicillin, and clarithromycin does not improve H. pylori eradication or symptoms when compared with quadruple therapy alone. This product provided B. longum, B. breve, Lacticaseibacillus casei, Lacticaseibacillus rhamnosus, Lactobacillus acidophilus, Lactobacillus delbrueckii subsp. bulgaricus, and Streptococcus thermophilus (90291). The lack of effect might be attributed to the shorter duration of therapy or the different composition and dose of probiotics.
• Hyperlipidemia. Oral Bifidobacterium longum has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in individuals with total cholesterol of 190 mg/dL or higher shows that taking fermented milk 375 grams containing B. longum BB536 and Lactobacillus acidophilus 145 for 4 weeks reduces low-density lipoprotein (LDL) cholesterol levels when compared with yogurt. However, high-density lipoprotein (HDL) cholesterol levels seem to be reduced as well (35401).
• Irritable bowel syndrome (IBS). Although most research shows that taking Bifidobacterium longum in combination with other probiotics is beneficial for IBS, the effect of B. longum alone is unclear. Details: Some clinical research shows that consuming B. longum (35624; Align or Bifantis) in daily doses of 100 million colony-forming units (CFUs) as capsules or 1 billion CFUs as capsules or a malted milk drink for 4-8 weeks reduces overall disease severity, abdominal pain, bloating, and bowel movement difficulty, an improves quality of life in patients with IBS when compared with placebo or to baseline. These benefits seem to occur within one week of treatment (13054,95392,111773). However, not all research agrees. A meta-analysis of a small number of clinical studies shows that although this strain reduces overall symptom severity, taking B. longum does not increase the frequency of global responders or reduce abdominal pain when compared with placebo (107594). Also, although a meta-analysis of two studies shows that taking B. longum 35624 along with multiple other probiotics reduces abdominal pain and bloating/distension, a meta-analysis of three clinical trials shows that taking B. longum 35624 alone does not improve these symptoms or bowel habit satisfaction (107593). Also, one clinical trial shows that taking B. longum R0175 10 billion CFUs daily for 8 weeks does not improve symptoms of IBS when compared with placebo (103440). One clinical study shows that taking B. longum NCC3001 10 billion CFUs once daily for 6 weeks increases the percentage of patients with IBS who experience a clinically meaningful improvement in anxiety and depression symptoms by about 2-fold when compared with placebo. A clinically meaningful improvement was defined as an increase in Hospital Anxiety and Depression (HAD) scale score of at least 2 points (95417). Some research has evaluated B. longum in combination with other probiotics. Clinical research shows that taking a specific product (Duolac Care) containing B. longum, Bifidobacterium breve, Bifidobacterium animalis subsp. lactis, Lactobacillus acidophilus, Lactiplantibacillus plantarum, Lacticaseibacillus rhamnosus, and Streptococcus thermophilus twice daily for 4 weeks can relieve symptoms in 72% of patients with IBS (95353). In addition, a clinical study in patients with diarrhea-predominant IBS shows that taking another specific combination probiotic (NordBiotic, MBM Biotix) containing B. longum BL020, B. breve BB010, B. animalis subsp. lactis BL040, Bifidobacterium bifidum BF030, Lactobacillus acidophilus LA120, Lacticaseibacillus rhamnosus LR110, Lacticaseibacillus paracasei LPC100, Lacticaseibacillus casei LC130, and Lactiplantibacillus plantarum LP140, and Streptococcus thermophilus ST250 2.5 billion CFUs daily twice daily for 8 weeks improves overall symptom severity, as well as pain severity, pain frequency, and quality of life when compared with placebo. Symptom severity was rated as mild by approximately 60% of those taking the probiotic mixture, compared with 30% of those taking placebo (107516).
• Japanese cedar pollinosis. It is unclear if oral Bifidobacterium longum is beneficial for this condition. Details: Some clinical research shows that taking powder containing B. longum BB536 50 billion colony-forming units twice daily for 4-13 weeks during pollen season reduces runny nose, nasal blockage, and overall symptom score when compared with placebo in patients with Japanese cedar pollen allergy (35382). However, other clinical research shows that taking this same strain daily for 13 weeks does not reduce runny nose or nasal blockage when compared with placebo (35379). There is also conflicting evidence regarding the effect of B. longum on eye symptoms, with some evidence showing no beneficial effect and other evidence suggesting reduced eye symptoms (35382,35384). Also, B. longum BB536 does not seem to improve nasal itching, sneezing, or throat symptoms associated with Japanese cedar pollinosis (35379,35382,35384).
• Lactose intolerance. Oral Bifidobacterium longum has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: In patients with persistent symptoms related to lactose intolerance despite a lactose-free diet, a small clinical trial shows that taking a combination of B. longum BB536 4 billion colony-forming units (CFUs), Lacticaseibacillus rhamnosus HN001 1 billion CFUs, and vitamin B6 1.4 mg (Zircombi) daily for 30 days modestly improves symptoms of bloating and constipation, but not abdominal pain, when compared with placebo (105153).
• Necrotizing enterocolitis (NEC). It is unclear if oral Bifidobacterium longum is beneficial or safe for NEC prevention. Details: Although some research disagrees, most clinical research and meta-analyses of clinical research show that giving bifidobacteria alone does NOT reduce the risk of NEC or all-cause mortality (92256,95344,95351,103437,105164). However, giving bifidobacteria in combination with lactobacilli or Enterococcus faecalis to preterm infants appears to reduce the risk of NEC by up to 87% and giving bifidobacteria with a prebiotic appears to reduce the risk of mortality (3162,90252,95351,102419,103437,103448,104157,105162,105164). A network meta-analysis of two clinical studies shows that taking a combination probiotic containing B. longum Bb-02, Bifidobacterium animalis subsp. Lactis Bb-12, and Streptococcus thermophilus TH-4, reduces the risk of NEC by 71% when compared with control (102437). Despite these findings, guidance among regulatory agencies and clinical organizations varies with respect to the use of probiotics in very low birth weight infants under 1000 grams. The US Food and Drug Administration (FDA) warns that preterm infants given probiotics are at risk of serious infections caused by the bacteria or fungi contained in probiotics due to cases reported in this group of infants (111610). Also, The American Academy of Pediatrics does not support the routine administration of probiotics to preterm infants, particularly those with a birth weight below 1000 grams, due to conflicting data on safety and efficacy and potential for harm in this vulnerable population (111608). The Canadian Paediatric Society, the American Gastroenterological Association, and the European Society for Paediatric Gastroenterology, Hepatology and Nutrition state that probiotic combinations may be of benefit in reducing the incidence of NEC in preterm neonates over 1000 grams. However, B. longum is not specifically recommended (103003,111609,111611). The effects of B. longum specifically are unclear.
• Nonalcoholic fatty liver disease (NAFLD). Oral Bifidobacterium longum has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical trial in patients with NAFLD shows that taking a combination product (Hexbio) containing B. longum BCMC 02129, B. longum BCMC 02120, Bifidobacterium bifidum BMCM 02290, Lactobacillus acidophilus BCMC 12,130, Lacticaseibacillus casei BCMC 12,313, and Lactobacillus delbrueckii subsp. lactis BCMC 12,451 as 30 billion colony-forming units twice daily for 6 months has no beneficial effects on hepatic steatosis or fibrosis, liver enzyme levels, blood lipids, or fasting blood glucose levels when compared with placebo (107523).
• Nonalcoholic steatohepatitis (NASH). Oral Bifidobacterium longum has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in patients with NASH shows that taking a specific combination probiotic capsule (Lactiale, Farmak) containing B. longum, Lacticaseibacillus casei, Lacticaseibacillus rhamnosus, Lactobacillus delbrueckii subsp. bulgaricus, and Streptococcus thermophilus 100 million colony-forming units in total, with fructo-oligosaccharides (FOS), once daily for 12 weeks does not improve liver enzyme levels or hepatic steatosis when compared with control (102415). However, other clinical research in patients with NASH undergoing lifestyle modification shows that taking an unspecified amount of B. longum in combination with FOS (Zirfos) daily for 24 weeks modestly reduces disease activity and steatosis, as well as levels of aspartate aminotransferase, low-density lipoprotein (LDL) cholesterol, insulin resistance, and inflammatory factors when compared with placebo. There was no effect on body mass index, high-density lipoprotein (HDL) cholesterol, triglycerides, other glycometabolic indices, or other measures of liver function (111849). It is unclear whether any benefits are related to B. longum, FOS, or the combination.
• Obesity. Although there has been interest in using oral Bifidobacterium longum for weight loss, there is insufficient reliable information about the clinical effects of B. longum for this use.
• Oral mucositis. Oral Bifidobacterium longum has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A clinical study in patients with locally advanced nasopharyngeal cancer undergoing radiochemotherapy shows that taking a specific probiotic product (Bifico, Shanghai Sine Pharmaceutical Co. Ltd.) containing B. longum, Lactobacillus delbrueckii subsp. lactis, and Enterococcus faecium three capsules twice daily for up to 7 weeks modestly reduces the incidence of severe oral mucositis when compared with placebo (102413).
• Periodontitis. Although there has been interest in using oral Bifidobacterium longum for periodontitis, there is insufficient reliable information about the clinical effects of B. longum for this condition.
• Postoperative infection. It is unclear if oral Bifidobacterium longum is beneficial for preventing postoperative infections. Details: Preliminary clinical research shows that taking B. longum BB536 50 billion colony-forming units daily for 7-14 days before colorectal surgery and then postoperatively for 14 days does not reduce the incidence of postoperative infections, the need for additional antibiotics, or the duration of hospital stay when compared with no intervention. However, hospital stay was reduced by 18 days in a sub-set of patients who had received preoperative chemoradiotherapy (111772).
• Prematurity. Oral Bifidobacterium longum has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One large observational study in infants fed strictly human milk, but not strictly formula or a combination, suggests that taking B. longum 1-1.5 billion colony-forming units with L. acidophilus during the first month of life for the prevention of necrotizing enterocolitis is associated with a modest increased weight gain velocity. The infants in this study were born between 22-29 weeks gestation and had a birthweight of less than 1500 grams (111771).
• Psoriasis. Oral Bifidobacterium longum has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in patients with psoriasis shows that taking a mixture of probiotics for 8 weeks modestly improves overall symptoms and feelings of depression when compared with placebo. The percentage of patients achieving at least a 50% or 75% reduction in overall symptom score was 40% and 24%, respectively, in those taking the probiotic, compared with 16% and 8% of those taking placebo. Each probiotic capsule provided a total daily dose of 2.6 billion colony-forming units (CFUs) of B. longum, Bifidobacterium bifidum, Bifidobacterium animalis subsp. lactis, and Lactobacillus acidophilus (107498).
• Radiation-induced diarrhea. Although there has been interest in using oral Bifidobacterium longum for radiation-induced diarrhea prevention, there is insufficient reliable information about the clinical effects of B. longum for this condition.
• Respiratory tract infections. It is unclear if oral Bifidobacterium longum is beneficial for preventing respiratory tract infections. Details: One clinical study shows that taking B. longum R0033 3 billion colony-forming units (CFUs) daily for 6 weeks does not reduce the percentage of college students who experience at least one day of cold or flu or the overall number of cold or flu episodes when compared with placebo (90272). However, preliminary clinical research in children aged 2-6 years shows that taking B. longum B536, 5 billion CFUs daily on 5 days each week for 10 months, reduces the duration of sore throat by 46% and modestly decreases the frequency of respiratory illnesses when compared with placebo. There was also a nonsignificant trend toward reduced fever and runny nose duration in the treatment group; however, the study was not adequately powered to detect a difference in these outcomes (98738).
• Retinopathy of prematurity. Oral Bifidobacterium longum has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One large observational study in premature infants suggests that taking L B. longum 1-1.5 billion colony-forming units with L. acidophilus during the first month of life for the prevention of necrotizing enterocolitis is not associated with a reduced risk of retinopathy of prematurity. The infants in this study were born between 22-29 weeks gestation and had a birthweight of less than 1500 grams (111771).
• Rotaviral diarrhea. Oral Bifidobacterium longum has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in hospitalized infants with rotaviral infection shows that giving a probiotic formula containing B. longum BORI and Lactobacillus acidophilus AD031 2 billion colony-forming units per gram twice daily for 3 days reduces the duration of diarrhea by about 1.2 days when compared with placebo; however, it does not reduce the duration of fever or the frequency of diarrhea or vomiting (95334).
• Sepsis. Oral Bifidobacterium longum has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One large observational study in infants fed a mix of human milk and formula, but not strictly human milk or formula, suggests that taking B. longum 1-1.5 billion colony-forming units with L. acidophilus during the first month of life for the prevention of necrotizing enterocolitis is associated with a 31% reduction in the development of clinical sepsis. The infants in this study were born between 22-29 weeks gestation and had a birthweight of less than 1500 grams (111771).
• Ulcerative colitis. It is unclear if oral Bifidobacterium longum is beneficial for ulcerative colitis. Details: A small clinical trial in patients with mild to moderate ulcerative colitis symptoms and using stable doses of standard treatment shows that taking at least 200 billion colony-forming units B. longum 536 three times daily for 8 weeks does not increase the proportion of patients in remission or reduce symptom severity when compared with taking placebo (111851). Given the high rate of response in the group given only standard treatment, this study may have been too small to detect differences between groups. More evidence is needed to rate Bifidobacterium longum for these uses.

(Read more about BIFIDOBACTERIUM LONGUM)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Antibiotic-associated diarrhea. Oral Lacticaseibacillus casei has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research shows that taking a specific L. casei-containing combination product (Bio-K+ CI1285) may be beneficial for preventing antibiotic-associated diarrhea. This combination product provides L. casei LBC80R, Lactobacillus acidophilus CL1285 and Lacticaseibacillus rhamnosus CLR2 as 100 billion colony-forming units (CFUs) daily (25494,95402,95403) However, taking L. casei might not help with the treatment of antibiotic-associated diarrhea. Clinical research in hospitalized patients with antibiotic-associated diarrhea shows that taking a combination of L. casei 20 million CFUs and Bifidobacterium breve 50 million CFUs 3 times daily does not reduce the average duration of diarrhea, the frequency of healing, or relapse rates, when compared with taking placebo (111006).
• Atopic dermatitis (eczema). Oral Lacticaseibacillus casei has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: In children under two years of age with atopic dermatitis who are on a cow's milk protein elimination diet, clinical research shows that taking a specific mixture (Latopic, Biomed S.A.) providing 1 billion colony-forming units (CFUs) of L. casei ôOCK 0919 50%, Lacticaseibacillus rhamnosus ŁOCK 0900 25%, and L. rhamnosus ôOCK 0908 25% for 3 months increases the odds of a 30% or greater improvement in symptom scores by about 2.6-fold when compared with placebo. However, there was no difference in the absolute symptom scores between groups. Beneficial effects of this combination were greater in children confirmed to have allergen sensitization (107510). Other clinical research in children ages 4-17 years shows that taking 1 billion CFUs of a 1:1:1 combination of L. casei CECT 9104, Bifidobacterium lactis CECT 8145, and Bifidobacterium longum CECT 7347 for 12 weeks modestly reduces symptom severity and the need for topical corticosteroids when compared with placebo (107531).
• Cancer. Although there has been interest in using oral Lacticaseibacillus casei for cancer prevention or treatment, there is insufficient reliable information about the clinical effects of L. casei for this condition.
• Clostridioides difficile infection. Some early research suggests that oral Lacticaseibacillus casei may be beneficial for preventing a first C. difficile infection. However, the quality of evidence is generally poor, and taking oral L. casei does not seem to be beneficial for the prevention of C. difficile recurrence. Details: Evidence from clinical and observational research investigating the effect of L. casei on C. difficile occurrence or recurrence is weak. Most studies use this species in combination with one or more additional probiotic species, including a specific product (Bio-K+ Cl1285) providing L. casei LBC80R and Lactobacillus acidophilus CL1285 and a specific product (Bio-K+ 50 Billion; Bio-K Plus International) providing L. casei LBC80R, L. acidophilus CL1285, and Lacticaseibacillus rhamnosus CLR2 as 50 or 100 billion CFUs daily (25494,90231,90934,95369,95403,107529). Observational research has found that providing a specific combination (Bio-K+ 50 Billion; Bio-K Plus International) of L. casei LBC80R, L. rhamnosus CLR2, and L. acidophilus CL1285 as 50-100 billion colony-forming units (CFUs) daily for 5 days to patients who are on antibiotics for at least 2 days reduces the hospital-wide incidence of C. difficile by approximately 40%. The incidence rate was decreased by at least 50% in the highest risk individuals taking this combination (107529). Current guidelines from the Infectious Diseases Society of America (IDSA) state that there is insufficient information to recommend administration of probiotics for the primary prevention of C. difficile-associated diarrhea (107538).
• Constipation. Oral Lacticaseibacillus casei has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Combinations of probiotics containing L. casei appear to increase stool frequency and improve symptoms of functional constipation in adults. These combinations include Hexbio, containing L. casei, Lactobacillus acidophilus, Lactobacillus delbrueckii subsp. lactis, Bifidobacterium bifidum, Bifidobacterium longum, and Bifidobacterium longum subsp. infantis 30 billion CFUs twice daily for 7 days (90266), and ID-HWS1000, containing L. casei IDCC 3451, Lactiplantibacillus plantarum IDCC 3501, Lacticaseibacillus rhamnosus IDCC 3201, Bifidobacterium animalis subsp. lactis IDCC 4301, Bifidobacterium breve IDCC 4401, Lactococcus lactis IDCC 2301, xylooligosaccharide, and dietary fiber as nondigestible maltodextrin, oat fiber, and psyllium husk fiber (107517).
• Depression. Oral Lacticaseibacillus casei has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in patients with major depression shows that taking L. casei, Lactobacillus acidophilus, and Bifidobacterium bifidum daily for 8 weeks reduces symptoms of depression measured on the Beck Depression Inventory (BDI) when compared with placebo (99780). However, the validity of the results from this study is limited by incomplete reporting. For example, patient baseline BDI scores were not reported.
• Diabetes. It is unclear if oral Lacticaseibacillus casei is beneficial for treatment of type 2 or gestational diabetes. Details: In patients with gestational diabetes, clinical research shows that taking a combination of freeze-dried L. casei, Lactobacillus acidophilus, and Bifidobacterium bifidum each as 2 billion colony-forming units (CFUs) per gram daily for 6 weeks improves fasting blood glucose levels and glycemic control when compared with placebo (95416,98430). Furthermore, a sub-analysis of a meta-analysis of clinical research investigating the effects of L. casei as part of multi-ingredient probiotic and prebiotic products shows that taking products containing L. casei modestly reduces fasting insulin levels and improves insulin resistance in this population. There were also modest reductions in triglyceride levels; however, the effects on fasting blood glucose were not significant (111796). It is unclear from these studies if any beneficial effects are related to L. casei, L. acidophilus, Bifidobacterium bifidum, or the combination. Limited evidence from mainly small clinical trials has also assessed the effects of L. casei for type 2 diabetes. In one study, taking L. casei 100 million CFUs daily for 8 weeks reduces fasting blood glucose by about 28 mg/dL when compared with placebo. There was no effect on glycated hemoglobin; however, the duration was inadequate to demonstrate an effect (99786). In another study, taking a specific product (Familact) containing L. casei and six other probiotic strains daily for 6 weeks reduces fasting blood glucose, but does not affect plasma insulin, when compared with placebo (99790).
• Diarrhea. Oral Lacticaseibacillus casei has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in children with dysentery being treated with ceftriaxone shows that taking a specific combination probiotic sachet (Kidilact, Zisttakhmir Company) containing L. casei, Lactobacillus acidophilus, Lacticaseibacillus rhamnosus, Lactobacillus delbrueckii subsp. bulgaricus, Bifidobacterium longum subsp. infantis, Bifidobacterium breve, and Streptococcus thermophilus daily for 5 days modestly reduces the duration of diarrhea, hospitalization, and blood in diarrhea when compared with control (102417). Although The European Society for Pediatric Infectious Diseases recommends probiotics in hospitalized children with diarrhea (98469) and the Infectious Disease Society of America (IDSA) recommends probiotics for the outpatient treatment of acute diarrhea (95388), both guidelines note that most evidence is low quality.
• Helicobacter pylori. It is unclear if oral Lacticaseibacillus casei is beneficial for H. pylori eradication in adults or children. Details: Clinical research in adults shows that taking L. casei along with six other probiotics in conjunction with bismuth quadruple therapy does not seem to improve H. pylori eradication rates when compared with placebo and bismuth quadruple therapy (90291). Also, taking a combination of L. casei and Lactobacillus acidophilus without any standard H. pylori therapies does not improve H. pylori eradication rates (12766). However, a clinical study in children shows that taking a fermented milk product containing L. casei DN-114 001 for 14 days along with triple therapy comprised of omeprazole, amoxicillin, and clarithromycin for 7 days improves the H. pylori eradication rate to approximately 85%, compared with 61% of those given triple therapy alone (107544).
• HIV/AIDS. Although there has been interest in using oral Lacticaseibacillus casei for HIV/AIDS, there is insufficient reliable information about the clinical effects of lactobacillus for this condition.
• Hyperlipidemia. It is unclear if oral Lacticaseibacillus casei is beneficial for hyperlipidemia. Details: In patients with primary hyperlipidemia, clinical research shows that taking L. casei 200 million colony-forming units in combination with red yeast rice twice daily for 8 weeks does not have beneficial effects on low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, or triglyceride levels, when compared with taking red yeast rice alone. Taking L. casei seems to modestly reduce diastolic blood pressure in this population; however, it is unclear if these changes are clinically significant (112517).
• Hypertension. It is unclear if oral Lacticaseibacillus casei is beneficial for lowering blood pressure. Details: A meta-analysis of 18 clinical trials shows that taking various species of lactobacilli as 100 million to 1.5 trillion colony-forming units daily for 3-24 weeks reduces systolic and diastolic blood pressure by 3 mmHg and 1.5 mmHg, respectively, when compared with placebo in various populations. However, sub-group analyses of three clinical trials show that these benefits do not occur in clinical research investigating the effects of L. casei, specifically (105135).
• Irritable bowel syndrome (IBS). Oral Lacticaseibacillus casei has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A clinical study in patients with diarrhea-predominant IBS shows that taking a specific multi-species probiotic (NordBiotic, MBM Biotix) containing L. casei LC130, Lacticaseibacillus rhamnosus LR110, Lacticaseibacillus paracasei LPC100, Lactobacillus acidophilus LA120, Lactiplantibacillus plantarum LP140, Bifidobacterium breve BB010, Bifidobacterium longum BL020, Bifidobacterium bifidum BF030, Bifidobacterium animalis subsp. lactis BL040, and Streptococcus thermophilus ST250 as 2.5 billion colony-forming units (CFUs) total twice daily for 8 weeks improves overall symptom severity, as well as pain severity, pain frequency, and quality of life, when compared with placebo. Symptom severity was rated as mild by approximately 60% of those taking the probiotic mixture, compared with 30% of those taking placebo (107516). However, clinical research shows that taking another multi-species combination of L. casei LBC80R, L. acidophilus CL1285, and L. rhamnosus CLR2 50 billion CFUs each daily for 3 months does not improve symptoms in patients with IBS when compared with placebo (99789).
• Lyme disease. Although there has been interest in using oral Lacticaseibacillus casei for Lyme disease, there is insufficient reliable information about the clinical effects of lactobacillus for this condition.
• Necrotizing enterocolitis (NEC). It is unclear if oral Lacticaseibacillus casei is beneficial or safe for NEC prevention. Details: Most meta-analyses of clinical research show that giving lactobacilli enterally reduces the risk of NEC and/or severe NEC in preterm, mainly very low birth weight (VLBW), infants. Some meta-analyses support the use of lactobacilli in combination with bifidobacteria, as opposed to lactobacilli alone for reducing the risk of NEC. However, the effects of L. casei specifically are unclear (95344,95351,103437,103445,104157,105162,105164). Also, guidance among regulatory agencies and clinical organizations varies with respect to the use of probiotics in very low birth weight infants under 1000 grams. The US Food and Drug Administration (FDA) warns that preterm infants given probiotics are at risk of serious infections caused by the bacteria or fungi contained in probiotics due to cases reported in this group of infants (111610). Also, The American Academy of Pediatrics does not support the routine administration of probiotics to preterm infants, particularly those with a birth weight below 1000 grams, due to conflicting data on safety and efficacy and potential for harm in this vulnerable population (111608). The Canadian Paediatric Society, the American Gastroenterological Association, and the European Society for Paediatric Gastroenterology, Hepatology and Nutrition state that probiotic combinations may be of benefit in reducing the incidence of NEC in preterm neonates over 1000 grams. However, L. casei is not specifically recommended (103003,111609,111611).
• Nonalcoholic fatty liver disease (NAFLD). Oral Lacticaseibacillus casei has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical trial in adults with NAFLD shows that taking a combination of L. casei BCMC 12,313, Lactobacillus acidophilus BCMC 12,130, Lactobacillus delbrueckii subsp. lactis BCMC 12,451, Bifidobacterium bifidum BCMC 02290, Bifidobacterium longum subsp. infantis BCMC 02129, and Bifidobacterium longum BCMC 02120 as 30 billion colony-forming units twice daily for 6 months has no beneficial effects on hepatic steatosis or fibrosis or on levels of liver enzymes, blood lipids, or fasting blood glucose, when compared with placebo (107523).
• Polycystic ovary syndrome (PCOS). Oral Lacticaseibacillus casei has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: In patients with PCOS, clinical research shows that taking a combination of L. casei T2 (IBRC-M10783), Lactobacillus acidophilus T16 (IBRC-M10785), and Bifidobacterium bifidum T1 (IBRC-M10771) as 2 billion colony-forming units (CFUs) each, plus inulin 800 mg, daily for 12 weeks modestly reduces serum insulin and triglyceride levels and improves insulin resistance and insulin sensitivity when compared with placebo. However, it does not alter cholesterol or fasting blood glucose levels (105159). Clinical research also shows that 31.3% of patients with PCOS taking L. casei in combination with other probiotics daily for 6 months had regular menstrual cycles compared with 12.5% of those taking placebo. There were also modest improvements in testosterone levels and waist circumference, but not other hormones, insulin resistance, body weight, or most measures of quality of life. The product provided L. casei UBLC-42 1 billion CFUs, along with Lactiplantibacillus plantarum UBLP-40, Lactobacillus acidophilus UBLA-34, Lacticaseibacillus casei UBLC-42, Limosilactobacillus fermentum UBLF-31, Lacticaseibacillus rhamnosus UBLR-58, Limosilactobacillus reuteri UBLRu-87, Bifidobacterium bifidum UBBB-55, and fructo-oligosaccharides (FOS) daily for 2 months and then twice daily for 4 months. All patients also underwent dietary and lifestyle changes (110974).
• Pregnancy-induced nausea and vomiting. Oral Lacticaseibacillus casei has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small preliminary clinical trial shows that taking probiotics during pregnancy reduces the severity and duration of nausea and vomiting by 16% to 54%. There was also a small benefit on stool hardness. A specific probiotic (Probiotics 10, Nature's Bounty) was taken as 2 capsules daily for two back-to-back cycles comprised of six days with probiotics and two days without. Each capsule contained a total of 10 billion colony-forming units (CFUs) of L. casei Lc-11, Lactiplantibacillus plantarum 299v and DSM 15312, Lactobacillus delbrueckii subsp. bulgaricus Lb-87, Lacticaseibacillus paracasei DSM 13434 and Lpc-37, Ligilactobacillus salivarius Ls-33, Levilactobacillus brevis Lbr-35, Lactobacillus acidophilus La-14, and Bifidobacterium animalis subsp. lactis Bl-04, along with inulin 200 mg (107199).
• Rheumatoid arthritis (RA). Small clinical studies suggest that taking Lacticaseibacillus casei might be beneficial for RA. Details: Two small clinical studies in patients with RA show that taking L. casei 01 as 100 million colony-forming units daily for 8 weeks reduces tender and swollen joints and increases the number of patients who experience moderate symptom improvement when compared with placebo (90230,90297). However, one small clinical study in patients with moderate-to-severe RA shows that taking capsules containing freeze-dried strains of L. casei, Lactobacillus acidophilus, and Bifidobacterium bifidum daily for 8 weeks does not reduce RA severity, the number of tender or swollen joints, or joint pain when compared with placebo (95418).
• Rotaviral diarrhea. It is unclear if Lacticaseibacillus casei is beneficial for rotaviral diarrhea. Details: Although the World Gastroenterology Organization has not made a recommendation (98471), the European Society for Pediatric Infectious Diseases recommends probiotics in hospitalized children with diarrhea (98469) and the Infectious Disease Society of America (IDSA) recommends probiotics for the outpatient treatment of acute diarrhea (95388). However, these guidelines note that most evidence is low quality and is not specific to rotavirus infection. Furthermore, these guidelines were released prior to the publication of the most recent, high-quality studies showing no benefit with the use of certain probiotics (98427,98428). Research on the use of L. casei, specifically, for this purpose is lacking.
• Short bowel syndrome. Although there has been interest in using oral Lacticaseibacillus casei for short bowel syndrome, there is insufficient reliable information about the clinical effects of L. casei for this condition.
• Small intestinal bacterial overgrowth (SIBO). It is unclear if oral Lacticaseibacillus casei is beneficial for the treatment of SIBO. Details: A small clinical study in children with chronic diarrhea due to SIBO shows that taking a combination of lyophilized L. casei 1.5 grams and Lactobacillus acidophilus 1.5 grams by mouth twice daily for 21 days decreases average daily stools by 1.5, but does not improve other symptoms, when compared with placebo (91143). Disparate study findings may be due to many factors, including differences in patient populations evaluated and use of different probiotic formulations. More evidence is needed to rate Lacticaseibacillus casei for these uses.

(Read more about LACTICASEIBACILLUS CASEI)

POSSIBLY EFFECTIVE

• Allergic rhinitis (hay fever). Oral live or heat-killed Lacticaseibacillus paracasei seems to improve some symptoms of allergic rhinitis in adults and children. Details: Clinical research in adults with persistent allergic rhinitis due to grass pollen despite treatment with loratadine shows that taking L. paracasei LP-33 as 2 billion colony-forming units (CFUs) daily for 5 weeks can improve quality of life by almost 18% when compared with placebo. The improvement in quality of life appears to be related to improvements in eye-related symptoms, but not nasal symptoms (90242). In children with perennial allergic rhinitis due to dust mites, taking L. paracasei LP-33 10 billion CFUs daily for 30 days improves quality of life related to overall symptom severity or level of bother by 28% and 23%, respectively, when compared to placebo. However, quality of life related specifically to nasal and eye-related symptoms was not improved when compared with placebo (107532). In children ages 2-5 years with allergic rhinitis, clinical research shows that taking fermented milk (Danone) containing L. paracasei DN-114 011 10 billion CFUs daily does not increase the time free from rhinitis episodes, the mean duration of episodes, or the cumulative number of episodes, when compared with taking a control milk. However, the number of episodes was reduced between months 3-9. The fermented milk was made with the yogurt cultures Lactobacillus delbrueckii subsp. bulgaricus and Streptococcus thermophilus (112512). Heat-killed L. paracasei has also been investigated. One clinical trial in adults with chronic allergy symptoms shows that taking heat-killed L. paracasei IJH-SONE68 1040 mg or 500,000 cells daily for 12 weeks modestly improves self-reported symptoms, including frequencies of sneezing and blowing, watery eyes, and head dullness, when compared with taking placebo. There was no effect on nasal congestion or itchy eyes (111939). Also, clinical research in children aged 5 years and older with perennial allergic rhinitis due to dust mites shows that taking heat-killed L. paracasei LP-33 10 billion cells daily for 30 days improves quality of life related to overall symptom severity or level of bother by 18% and 22%, respectively, when compared with placebo. Efficacy was not inferior to live L. paracasei LP-33 (107532).
• Atopic dermatitis (eczema). Oral live Lacticaseibacillus paracasei, alone or in combination with other probiotics, seems to be beneficial for the treatment of atopic dermatitis in infants and children and for preventing atopic dermatitis when provided to the infant after exposure during pregnancy. Small clinical trials suggest that heat-killed L. paracasei does not seem to be beneficial for the treatment of atopic dermatitis. Details: In children aged 1-18 years, clinical research shows that taking L. paracasei 2 billion colony-forming units (CFUs) daily, alone or with Limosilactobacillus fermentum 2 billion colony-forming units (CFUs) daily each, for 3 months modestly reduces symptoms of atopic dermatitis when compared with placebo (98440). However, another clinical trial shows that administering formula containing lyophilized L. paracasei CNCM I-2116 to infants aged 3-6 months does not reduce atopic dermatitis severity or the prevalence of atopic dermatitis after 12 weeks of treatment (90256). Heat-killed L. paracasei has also been investigated. In adults treated with conventional topical corticosteroid and tacrolimus, a small clinical trial shows that taking heat-killed L. paracasei K71 200 billion cells daily for 12 weeks does not improve skin symptom severity, quality of life, or use of topical medication, when compared with taking placebo (111947). Also, in infants ages 4-30 months with atopic dermatitis, clinical research shows that, in addition to topical fluticasone propionate cream, taking heat-treated L. paracasei GM-080 daily for 16 weeks does not further improve symptoms when compared with using the topical fluticasone propionate cream alone (102406). Other clinical research has investigated the effects of L. paracasei in combination with other probiotics for the PREVENTION of atopic dermatitis. A combination of L. paracasei, Ligilactobacillus salivarius, Bifidobacterium animalis subsp. lactis, and Bifidobacterium bifidum, a total of 10 billion CFUs daily provided from 36 weeks' gestation and then to the infant until age 6 months, reduces the prevalence of atopic dermatitis at age two by approximately 60% (90234). Similar findings occurred in clinical research investigating the effect of L. paracasei ST11 and B. longum BL999 (ST11+BL999) for the last 2 months of pregnancy and first 2 months of breastfeeding (90234,90285).
• Common cold. A combination of Lacticaseibacillus paracasei and Lactiplantibacillus plantarum seems to be beneficial for reducing the incidence or severity of the common cold. The effects of L. paracasei alone are unclear. Details: Clinical research in healthy individuals shows that taking an acidified milk drink providing L. paracasei (L. casei 431) 1 billion colony-forming units (CFUs) daily for 21 days before and after receiving the seasonal influenza vaccination does not affect the number, duration, or severity of common cold or influenza-like illness episodes when compared with taking placebo. However, there was a modest reduction in the duration of illness 4-6 weeks after vaccination (111937). L. paracasei has also been examined in combination with L. plantarum. Clinical research shows that taking L. plantarum HEAL 9 (DSM 15312) and L. paracasei 8700:2 (DSM 13434) (Probi Defendum, Probi AB) 1 billion CFUs daily for 12 weeks reduces the incidence of the common cold by about 12% and reduces the number of symptomatic days from 8.6 to 6.2 when compared with placebo (17119). Additional clinical research in adults at increased risk of a common cold shows that taking this same combination for 12 weeks does not reduce the incidence of developing a common cold when compared with placebo. However, symptom severity was modestly reduced. Also, each episode was reduced by an average of 1.1 days (107557). A more recent clinical study in adults at increased risk of developing a common cold shows that taking the same combination does not reduce symptom severity or the absolute number of common cold episodes when compared with placebo. However, in individuals with at least one cold, the mean number of colds was reduced by 0.12 over the 12-week period. In addition, there were modest overall reductions in the incidence of recurring colds and the use of analgesics (107555). A smaller clinical trial using the same product at the same dose and duration has also been conducted in children aged 1-6 years in daycare. The severity of nasal congestion/runny nose was modestly reduced when compared with placebo in this population. However, there were no differences between groups in the overall incidence, severity, or duration of common colds or upper respiratory tract infections or the number of days absent from daycare (107556). This latter trial was terminated prior to the completion of the planned patient recruitment for reasons unrelated to adverse effects, which may have impacted the findings. L. paracasei has also been investigated as part of fermented milk. A clinical trial in elderly nursing home residents shows that drinking two bottles of fermented milk containing L. paracasei Shirota daily for 6 months does not reduce the risk of developing respiratory symptoms when compared with placebo milk (96885). However, a small clinical study in healthy, male, middle-aged office workers shows that drinking a fermented milk made with L. paracasei Shirota for 12 weeks reduces the incidence and duration of the common cold by 59% when compared with a control milk (98426). Also, a clinical study in children aged 3-6 years attending daycare shows that drinking a fermented milk product containing L. paracasei (Actimel, Danone) 200 grams daily for 3 months reduces the risk of developing the common cold, the most common upper respiratory tract infection in these children, by around 18% when compared with a control milk product. The fermented milk product did not affect medication use or sick leave from daycare (96882).

POSSIBLY INEFFECTIVE

• Constipation. Oral Lacticaseibacillus paracasei does not seem to be beneficial for constipation. Details: Meta-analyses of two or three clinical trials in adults with functional constipation show that taking L. paracasei Shirota 6.5-30 billion colony-forming units daily for 4 weeks does not appear to improve gut transit time or increase the number of stools (95342). Also, clinical research in patients with constipation shows that taking a combination of L. paracasei Lpc-37 2.5 billion colony-forming units daily for 2 weeks along with Lactobacillus acidophilus NCFM and Bifidobacterium animalis subsp. lactis strains Bl-04, Bi-07, and HN019, does not improve bloating, abdominal pain, intestinal transit time, frequency of bowel movements, or stool consistency when compared with placebo. There was a small beneficial effect on flatulence (110979).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Acne. It is unclear if topical heat-killed Lacticaseibacillus paracasei is beneficial for acne. Details: Preliminary clinical research in patients with mild to moderate acne shows that topical application with a lotion providing the cell-free supernatant of L. paracasei MSMC 39-1 twice daily for 4 weeks is as effective as a lotion containing 2.5% benzoyl peroxide for decreasing redness and the inflammatory acne lesion count. There was no effect of either lotion of non-inflammatory acne lesion count (111945). This study is limited by the lack of blinding to lotion type.
• Alcohol-related liver disease. It is unclear if oral Lacticaseibacillus paracasei is beneficial in patients with alcohol-related liver disease. Details: Clinical research in patients with alcohol-related liver disease shows that taking fermented milk providing L. paracasei Shirota daily for 60 days reduces levels of triglycerides and low-density lipoprotein (LDL) cholesterol by 27% and 24%, respectively, compared with taking placebo. There was also an improvement in liver function, based on modest improvements in various liver markers, including alanine aminotransferase, aspartate aminotransferase, gamma-glutamyltransferase, and bilirubin. Patients consumed L. paracasei 20 billion colony-forming units daily (111958).
• Antibiotic-associated diarrhea. It is unclear if oral Lacticaseibacillus paracasei is beneficial for preventing antibiotic-induced diarrhea. Details: Most clinical research has investigated the effect of L. paracasei in combination with other probiotics. A meta-analysis of 3 clinical trials in hospitalized or outpatient adults shows that taking L. paracasei in combination with up to 8 other probiotic strains reduces the risk of AAD by 40% when compared with taking placebo (107635). One of these studies, a small clinical trial in patients taking amoxicillin 500 mg twice daily for 7 days, used a specific combination probiotic (Ecologic AAD) twice daily for 14 days. The product provided L. paracasei NIZO 3672, Bifidobacterium bifidum NIZO 3804, Bifidobacterium animalis subsp. lactis NIZO 3680, Enterococcus faecium NIZO 3886, Lactobacillus acidophilus NIZO 3678 and NIZO 3887, Lactiplantibacillus plantarum NIZO 3684, Lacticaseibacillus rhamnosus NIZO 3689, and Ligilactobacillus salivarius NIZO 3675 as 1 billion colony-forming units (CFUs) each daily (95405). In addition, one small clinical study in hospitalized adults shows that consuming a 97 mL drink (Actimel, Danone) containing L. paracasei 100 CFUs/mL, Streptococcus thermophilus 100 million CFUs/mL, and Lactobacillus delbrueckii subsp. bulgaricus 10 million CFUs/mL twice daily while taking antibiotics reduces the odds of developing AAD by 75% when compared with a milkshake without probiotics (16740). However, an additional large clinical trial in children aged 3 months and up shows that taking L. paracasei in combination with other probiotics does not reduce the risk of antibiotic-associated diarrhea when compared with taking placebo, when the more stringent definition is considered excluding diarrhea of other etiologies. However, the risk of diarrhea of any etiology is reduced by 35%. The probiotic supplement provided a total of 10 billion CFUs of L. paracasei W20, Lactobacillus acidophilus W37, Lactobacillus acidophilus W55, Bifidobacterium bifidum W23, Bifidobacterium animalis subsp. lactis W51, Lactiplantibacillus plantarum W62, Lacticaseibacillus rhamnosus W71, and Ligilactobacillus salivarius W24 daily from the first day of antibiotic treatment until 7 days after treatment ended (110969). It is unclear if any benefits are due to L. paracasei, the other ingredients, or their combination. L. paracasei has also been investigated alone. In hospitalized patients with spinal cord injury, preliminary clinical research shows that 17.1% of patients taking L. paracasei Shirota 6.5 billion CFUs daily in a probiotic drink (Yakult light) developed diarrhea compared with 54.9% of those given only routine care. L. paracasei was taken during antibiotic treatment and for an additional 7 days (111955). This study is limited by a lack of blinding.
• Antituberculosis treatment-associated adverse effects. It is unclear if oral Lacticaseibacillus paracasei is beneficial for preventing adverse effects associated with antituberculosis treatment. Details: Preliminary clinical research shows that taking L. paracasei Shirota 10 billion or 20 billion colony-forming units (CFUs) daily during standard antituberculosis treatment does not reduce the incidence of liver injury when compared with antituberculosis treatment alone. However, there was a modest decrease in the incidence of elevated alkaline phosphatase in patients taking 20 billion CFUs daily and a modest decrease in the incidence of elevated bilirubin in patients taking 10 billion CFUs daily. There was no effect on other liver markers (107509). Other preliminary clinical research shows that taking this same dose daily for 2 months during standard antituberculosis treatment reduces the rate of any gastrointestinal adverse event to 29% to 38% of patients, compared with 50% of those taking antituberculosis treatment alone. In addition, the duration of symptoms was shorter. However, when individual gastrointestinal adverse events were evaluated, only the incidence and duration of vomiting and appetite loss were reduced; the incidence of nausea, diarrhea, flatulence, and constipation were unaffected (107542).
• Asthenopia (eye strain). It is unclear if oral heat-killed Lacticaseibacillus paracasei is beneficial for asthenopia. Details: Preliminary clinical research shows that taking heat-killed L. paracasei 50 mg daily for 8 weeks does not decrease eye fatigue induced by blue-light emitting devices when compared with placebo. However, a subgroup analysis shows that in patients who report eye fatigue at baseline, subjective symptoms of eye fatigue and eye redness are reduced after exposure to blue-light emitting devices (98429).
• Asthma. It is unclear if oral Lacticaseibacillus paracasei is beneficial for asthma. Details: A small clinical study in children with asthma shows that taking L. paracasei GMNL-133 (LP) 2 billion colony-forming units (CFUs), Limosilactobacillus fermentum GM-090 (LF) 2 billion CFUs, or both strains together daily for 3 months seems to modestly reduce asthma severity and increase Childhood Asthma Control Test (C-ACT) scores when compared with placebo (99785). In children ages 2-5 years with asthma, clinical research shows that taking fermented milk (Danone) containing L. paracasei DN-114 011 10 billion colony-forming units daily does not increase the time free from asthma episodes, the mean duration of episodes, or the cumulative number of episodes, when compared with taking a control milk. The fermented milk was made with the yogurt cultures Lactobacillus delbrueckii subsp. bulgaricus and Streptococcus thermophilus (112512).
• Cancer. Although there has been interest in using oral Lacticaseibacillus paracasei for cancer prevention or treatment, there is insufficient reliable information about the clinical effects of L. paracasei for this condition.
• Canker sores. Oral Lacticaseibacillus paracasei has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical trial shows that taking a combination of L. paracasei, Lacticaseibacillus rhamnosus, Lactobacillus acidophilus, and Bifidobacterium animalis subsp. lactis modestly reduces pain, but not the number of lesions or healing time, when compared with placebo (107548).
• Clostridioides difficile infection. Although there has been interest in using oral Lacticaseibacillus paracasei for C. difficile infection prevention, there is insufficient reliable information about the clinical effects of L. paracasei for this condition.
• Colic. Although there has been interest in using oral Lacticaseibacillus paracasei for colic, there is insufficient reliable information about the clinical effects of L. paracasei for this condition.
• Colorectal cancer. It is unclear if oral Lacticaseibacillus paracasei is beneficial for colorectal cancer prevention. Details: Clinical research in patients with previous removal of colorectal tumors shows that taking at least 1.5 billion colony-forming units L. paracasei Shirota 3 times daily for 4 years does not prevent the development of new colorectal tumors when compared with not taking L. paracasei. However, taking L. paracasei reduces the occurrence of colorectal tumors with moderate or severe atypia by 35%. Half of the patients included in this research were also consuming wheat bran biscuits (111959).
• Dental caries. It is unclear if oral Lacticaseibacillus paracasei is beneficial for dental caries prevention. Details: Preliminary clinical research shows that giving infants a weaning cereal containing L. paracasei F19 (Semper AB) from 4 months of age until 13 months of age does not reduce the risk of dental caries in the primary or permanent teeth by the age of 3, 6, or 9 years (90260).
• Depression. Although there has been interest in using oral Lacticaseibacillus paracasei for depression, there is insufficient reliable information about the clinical effects of L. paracasei for this condition.
• Diabetes. Oral Lacticaseibacillus paracasei has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in patients with gestational diabetes shows that taking a specific product containing L. paracasei and other probiotics (Visbiome, ExeGi Pharma) as a total of 112.5 billion colony-forming units (CFUs) twice daily for 8 weeks does not affect levels of fasting blood glucose or glycated hemoglobin (HbA1c) when compared with placebo. However, there were small improvements in insulin levels and insulin resistance (107549). This same combination probiotic has also been evaluated in children 2-12 years of age with new-onset type 1 diabetes. One clinical study shows that taking Visbiome as 112.5 billion CFUs daily for 3 months modestly decreases HbA1c and insulin requirements when compared with placebo. Also, about three times as many children achieved remission, defined as insulin requirements of less than 0.5 U/kg daily and HbA1c of less than 7%. However, C-peptide levels and the maintenance of residual pancreatic beta-cell function were not affected when compared with placebo (107497).
• Diarrhea. It is unclear if oral Lacticaseibacillus paracasei is beneficial for the treatment of diarrhea. Details: While the European Society for Pediatric Infectious Diseases recommends probiotics in hospitalized children with diarrhea (98469) and the Infectious Disease Society of America (IDSA) recommends probiotics for the outpatient treatment of acute diarrhea (95388), both guidelines note that most evidence is low quality. Also, evidence related to the use of L. paracasei, specifically, is limited. One large clinical study shows that taking a fermented milk product containing L. paracasei DN-114 001 (e.g., DanActive, Dannon) 100 million CFUs per milliliter for up to 4 months helps to prevent acute, non-rotaviral diarrhea in children ages 6-24 months (14374).
• Exercise-induced muscle damage. It is unclear if oral Lacticaseibacillus paracasei is beneficial for exercise-induced muscle damage. Details: Clinical research in adults shows that taking L. paracasei L-PS23 20 billion colony-forming units or heat-killed L. paracasei HK-PS23 20 billion cells daily modestly reduces muscle strength loss and improves measures of muscle recovery in the 48 hours following exercise-induced muscle damage when compared with taking placebo. L. paracasei was taken for 6 weeks prior to inducing muscle damage and continued for an additional 48 hours (111940).
• Exercise-induced respiratory infections. It is unclear if oral Lacticaseibacillus paracasei is beneficial for preventing respiratory infections related to exercise. Details: Clinical research in endurance athletes shows that taking a probiotic supplement containing L. paracasei Shirota (LCS, Yakult) 65 billion colon-forming units (CFUs) twice daily for 20 weeks does not reduce the risk of developing an upper respiratory tract infection when compared with placebo. Taking this probiotic also does not reduce the duration or severity of respiratory infections in this population (98431). However, other clinical research shows that taking L. paracasei Shirota 6.5 billion CFUs daily for 4 months during winter endurance training modestly reduces the proportion of athletes with at least 1 week with upper respiratory tract illness symptoms by 27%, and the total number of episodes by 0.9, when compared with taking placebo. There was no difference in symptom severity or duration (111950).
• Fractures. It is unclear if oral Lacticaseibacillus paracasei is beneficial for the healing of fractures. Details: A clinical study in elderly adults with distal radius fracture shows that consuming 100 mL of skim milk containing L. paracasei Shirota 12 billion colony-forming units twice daily for 3 months modestly improves hand function, pain, and daily life activities when compared with skimmed milk placebo (102407). This study is limited by the fact that, although subjective measures showed improvement, there was no consistent improvement in objective measures.
• Helicobacter pylori. It is unclear if oral Lacticaseibacillus paracasei is beneficial in children with H. pylori infection. Details: Clinical research in H. pylori-colonized children aged 6 to 17 years shows that taking a fermented dairy product containing live or heat-killed L. paracasei ST11 (Chamyto, Nestle'-Chile SA, Santiago, Chile) 1.6 billion cells or colony-forming units 5 days each week for 4 weeks does not reduce H. pylori colonization when compared with the beverage without L. paracasei. The beverages were fermented with Lactobacillus helveticus (110934).
• HIV/AIDS. Although there has been interest in using oral Lacticaseibacillus paracasei for HIV/AIDS, there is insufficient reliable information about the clinical effects of L. paracasei for this condition.
• Hypercholesterolemia. It is unclear if oral Lacticaseibacillus paracasei is beneficial for hypercholesterolemia. Details: A small clinical trial in patients with hypercholesterolemia shows that taking 10.5 billion colony-forming units of L. paracasei TISTR 2593 daily for 90 days reduces levels of low-density lipoprotein cholesterol by about 11% when compared with taking placebo. There was no effect on total or high-density lipoprotein cholesterol or triglyceride levels (111938).
• Insomnia. It is unclear if oral Lacticaseibacillus paracasei is beneficial for improving sleep quality. Details: A small clinical trial in students shows that taking fermented milk containing L. paracasei Shirota daily for 11 weeks, starting 8 weeks prior to a stressful standardized examination, modestly reduces feelings of sleepiness upon rising and increases sleep length when compared with a non-fermented placebo milk. Objective measures of sleep latency were also reduced. There was no effect on total sleep time or sleep efficacy (111949).
• Irritable bowel syndrome (IBS). It is unclear if oral Lacticaseibacillus paracasei is beneficial for IBS. Details: One clinical study shows that taking a specific multi-species probiotic (Visbiome, ExeGi Pharma) containing L. paracasei and seven other probiotics as 450 billion colony-forming units (CFUs) daily in two divided doses for 8 weeks improves abdominal bloating, but not abdominal pain, flatulence, or number of stools, in patients with diarrhea-predominant IBS (IBS-D) (11379). However, adding this product as 900 billion CFUs daily to a sham diet or a low-FODMAP diet for 4 weeks does not improve IBS symptoms when compared with placebo (98741). Another clinical study in patients with IBS-D shows that taking a specific multi-species probiotic (NordBiotic, MBM Biotix) containing L. paracasei LPC100, Lacticaseibacillus rhamnosus LR110, Lactobacillus acidophilus LA120, Lacticaseibacillus casei LC130, and Lactiplantibacillus plantarum LP140, Bifidobacterium breve BB010, Bifidobacterium longum BL020, Bifidobacterium bifidum BF030, Bifidobacterium animalis subsp. lactis BL040, and Streptococcus thermophilus ST250 as 2.5 billion CFUs total twice daily for 8 weeks improves overall symptom severity, as well as pain severity, pain frequency, and quality of life when compared with placebo. Symptom severity was rated as mild by approximately 60% of those taking the probiotic mixture, compared with 30% of those taking placebo (107516). However, other clinical research shows that taking L. paracasei HA-196 10 billion CFUs daily or L. paracasei Shirota 13 billion CFUs daily for 8 weeks or a combination of L. paracasei, L. acidophilus, and B. animalis subsp. lactis BB-12 (Cultura) 13-20 billion CFUs daily for 6 months does not improve most symptoms of IBS (90236,94696,94697,103440,111952). L. paracasei has also been examined in combination with other ingredients. In patients 60 years and older with IBS, taking L. paracasei DKGF1 100 billion CFUs daily with Opuntia humifusa extract more than doubles the proportion of patients with improvements in self-reported overall symptoms during more than 2 of the 4 weeks of treatment when compared with taking placebo. Response rates for abdominal pain and psychological well-being were also improved. However, there were no differences between groups for response rates related to improvements in gas or bloating (111943).
• Japanese cedar pollinosis. It is unclear if oral Lacticaseibacillus paracasei is beneficial for Japanese cedar pollinosis. Details: Clinical research in patients with Japanese cedar pollinosis shows that taking L. paracasei KW3110 at least one trillion colony-forming units daily for 12 weeks starting 1 month before the start of the pollen season does not improve nasal symptoms during peak season when compared with taking placebo (111948).
• Lower respiratory tract infections. Oral Lacticaseibacillus paracasei has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in children ages 3-6 years shows that taking taking fermented milk (DanActive, Dannon) containing L. paracasei DN-114 011 20 billion colony-forming units daily for 90 days does not prevent lower respiratory tract infections when compared with taking a control non-fermented milk. The fermented milk was made with the yogurt cultures Lactobacillus delbrueckii subsp. bulgaricus and Streptococcus thermophilus (112515).
• Lyme disease. Although there has been interest in using oral Lacticaseibacillus paracasei for Lyme disease, there is insufficient reliable information about the clinical effects of L. paracasei for this condition.
• Migraine headache. It is unclear if oral Lacticaseibacillus paracasei is beneficial for migraine treatment. Details: Clinical research in patients with moderate to severe vestibular symptoms associated with migraine headaches shows that taking L. paracasei Shirota 20 billion colony-forming units daily for 4 months modestly reduces symptoms of vertigo and dizziness. The number of attacks with vertigo each week was reduced by 1.6, compared with 0.9 in patients taking placebo. Both vertigo and dizziness severity, as well as feelings of anxiety and depression, were also modestly reduced (111951). Although changes in these endpoints were statistically significant after 4 months, there were no differences between endpoints after 2 months, and the clinical significance is unclear.
• Necrotizing enterocolitis (NEC). It is unclear if oral Lacticaseibacillus paracasei is beneficial or safe for NEC prevention. Details: Most meta-analyses of clinical research show that giving lactobacilli enterally reduces the risk of NEC and/or severe NEC in preterm, mainly very low birth weight (VLBW), infants. Some meta-analyses support the use of lactobacilli in combination with bifidobacteria, as opposed to lactobacilli alone for reducing the risk of NEC. However, the effects of L. paracasei, specifically, are unclear (95344,95351,103437,103445,104157,105162,105164). Also, guidance among regulatory agencies and clinical organizations varies with respect to the use of probiotics in very low birth weight infants under 1000 grams. The US Food and Drug Administration (FDA) warns that preterm infants given probiotics are at risk of serious infections caused by the bacteria or fungi contained in probiotics due to cases reported in this group of infants (111610). Also, The American Academy of Pediatrics does not support the routine administration of probiotics to preterm infants, particularly those with a birth weight below 1000 grams, due to conflicting data on safety and efficacy and potential for harm in this vulnerable population (111608). The Canadian Paediatric Society, the American Gastroenterological Association, and the European Society for Paediatric Gastroenterology, Hepatology and Nutrition state that probiotic combinations may be of benefit in reducing the incidence of NEC in preterm neonates over 1000 grams. However, L. paracasei is not specifically recommended (103003,111609,111611).
• Nonalcoholic fatty liver disease (NAFLD). Oral Lacticaseibacillus paracasei has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in patients with NAFLD shows that taking 2 sachets daily for 3 months of a specific combination product (VSL#3) containing L. paracasei and other probiotics modestly decreases triglyceride levels and liver enzymes when compared with taking placebo. However, there was no change in body mass index or most glycemic or lipid parameters (111009). The effect of L. paracasei alone is unclear from this study.
• Osteoarthritis. It is unclear if oral Lacticaseibacillus paracasei is beneficial for osteoarthritis. Details: A large clinical trial in patients with mild to moderate symptoms of knee osteoarthritis shows that taking skim milk containing L. paracasei Shirota 6 billion colony-forming units twice daily for 6 months modestly improves stiffness, pain, and function when compared with taking skim milk placebo (111953). More research is needed to determine whether L. paracasei Shirota is as effective as standard medications.
• Pain (acute). It is unclear if oral Lacticaseibacillus paracasei is beneficial for acute pain. Details: Clinical research in patients with a single rib fracture shows that taking skim milk containing L. paracasei Shirota 6 billion colony-forming units daily for 1 month modestly reduces pain during deep breathing, coughing, and turning over when compared with taking skim milk placebo. Good pain relief during these situations, defined as a decline in maximal pain intensity of 3 points on a 10-point scale, occurred in 42.1% to 61.6% of patients, compared with 25.9% to 47.3% of patients taking placebo. However, there was no effect on sleep quality (111957).
• Parkinson disease. It is unclear if oral Lacticaseibacillus paracasei is beneficial for Parkinson disease. Details: Clinical research in patients with Parkinson disease shows that taking fermented milk providing L. paracasei Shirota 10 billion colony-forming units daily for 12 weeks reduces the use of laxatives by 0.37 or 15% per week and modestly improves stool consistency and symptoms of constipation when compared with taking an acidified milk placebo. There were also modest improvements in non-motor symptoms, anxiety, and depression, but not overall disease severity or dopaminergic therapy requirement (111956).
• Postoperative infection. Although there has been interest in using oral Lacticaseibacillus paracasei for preventing postoperative infections, there is insufficient reliable information about the clinical effects of L. paracasei for this purpose.
• Pouchitis. Oral Lacticaseibacillus paracasei has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research shows that continuous oral treatment for one year with a specific combination product (Visbiome, ExeGi Pharma) containing L. paracasei and other probiotics, 6 grams (300-500 billion live bacteria per gram) daily, for up to 12 months seems to maintain remission in 85% of patients with pouchitis (6087,12769).
• Pregnancy-induced nausea and vomiting. Oral Lacticaseibacillus paracasei has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small preliminary clinical trial shows that taking probiotics during pregnancy reduces the severity and duration of nausea and vomiting by 16% to 54%. There was also a small benefit on stool hardness. A specific probiotic (Probiotics 10, Nature's Bounty) was taken as 2 capsules daily for two back-to-back cycles of six days with probiotics and two days without. Each capsule contained a total of 10 billion colony-forming units (CFUs) of L. paracasei DSM 13434 and Lpc-37, Lactiplantibacillus plantarum 299v and DSM 15312, Lactobacillus delbrueckii subsp. bulgaricus Lb-87, Ligilactobacillus salivarius Ls-33, Levilactobacillus brevis Lbr-35, Lactobacillus acidophilus La-14, Lacticaseibacillus casei Lc-11, and Bifidobacterium animalis subsp. lactis Bl-04, along with inulin 200 mg (107199).
• Prostatitis. It is unclear if oral Lacticaseibacillus paracasei is beneficial for prostatitis. Details: Preliminary clinical research in adults with chronic bacterial prostatitis who are receiving antibiotic treatment shows that taking L. paracasei CNCM I-1572 (L. casei DG) one capsule twice daily for 6 months improves clinical symptoms over baseline in 73% of patients and also reduces symptomatic recurrence and antibiotic use (105133). The validity of these findings is limited by the lack of a comparator group.
• Proton pump inhibitor-induced gastrointestinal (GI) symptoms. It is unclear if oral Lacticaseibacillus paracasei is beneficial for preventing GI symptoms in patients using proton pump inhibitors. Details: Preliminary clinical research in patients with gastroesophageal reflux disease shows that taking L. paracasei F19 (Genefilus F19, Siffra Farmaceutici S.r.l., Italy) 24 billion colony-forming units 3 times a week for 3 or 6 months during treatment with pantoprazole 40 mg daily modestly reduces stool frequency and the severity and proportion of patients with flatulence and bloating when compared with taking placebo (111941).
• Radiation-induced diarrhea. Oral Lacticaseibacillus paracasei has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical trial in patients undergoing pelvic radiotherapy shows that taking 96 mL fermented milk (Danone) 3 times daily containing L. paracasei DN-114 001 100 million colony-forming units per gram starting one week before the initiation of radiation treatment does not delay the development of diarrhea when compared with taking a control sterilized milk product. The fermented milk was continued throughout treatment and made with the yogurt cultures Lactobacillus delbrueckii subsp. bulgaricus and Streptococcus thermophilus (112513).
• Rotaviral diarrhea. It is unclear if oral Lacticaseibacillus paracasei is beneficial for rotaviral diarrhea. Details: The current guidelines related to the treatment of viral diarrhea are conflicting. While the World Gastroenterology Organization has not made a recommendation (98471), the European Society for Pediatric Infectious Diseases recommends probiotics in hospitalized children with diarrhea (98469) and the Infectious Disease Society of America (IDSA) recommends probiotics for the outpatient treatment of acute diarrhea (95388). However, these guidelines note that most evidence is low quality and is not specific to rotavirus infection. Furthermore, these guidelines were released prior to the publication of the most recent, high-quality studies showing no benefit with the use of certain probiotics (98427,98428). Also, research on the use of L. paracasei, specifically, is lacking.
• Sarcopenia. Although there has been interest in using oral Lacticaseibacillus paracasei for sarcopenia prevention, there is insufficient reliable information about the clinical effects of L. paracasei for this purpose.
• Short bowel syndrome. Although there has been interest in using oral Lacticaseibacillus paracasei for short bowel syndrome, there is insufficient reliable information about the clinical effects of L. paracasei for this condition.
• Small intestinal bacterial overgrowth (SIBO). It is unclear if oral Lacticaseibacillus paracasei is beneficial for the treatment of SIBO. Details: One preliminary clinical study in adults with irritable bowel syndrome and a recent diagnosis of SIBO shows that consuming 65 mL of a specific product (Yakult, Yakult Ltd.) providing 6.5 billion colony-forming units (CFUs) of L. paracasei Shirota by mouth daily for 6 weeks modestly improves flatulence, but not other symptoms, when compared to baseline (91144).
• Ulcerative colitis. Oral Lacticaseibacillus paracasei has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: The best evidence of benefit is for a specific combination product (Visbiome, ExeGi Pharma). Doses of 3 grams (equivalent to 900 billion colony-forming units (CFUs)) once or twice daily have been used in combination with conventional treatment. In children aged 1-16 years, doses of 450-1800 billion CFUs for up to one year have been used (3261,14370,14371,16841,95337). A meta-analysis of clinical research shows that taking this product as an adjunct to standard ulcerative colitis treatment can increase remissions rates in adults and children by about 1.7-fold when compared with standard treatment alone (95337). There is also evidence that it is beneficial for improving remission rates in patients who do not adequately respond to conventional treatment (14371).
• Upper respiratory tract infection (URTI). Oral Lacticaseibacillus paracasei has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in children ages 3-6 years shows that taking taking fermented milk (DanActive, Dannon) containing L. paracasei DN-114 011 20 billion colony-forming units daily for 90 days reduces the incidence of URTIs by 18% when compared with taking a control non-fermented milk. The fermented milk was made with the yogurt cultures Lactobacillus delbrueckii subsp. bulgaricus and Streptococcus thermophilus (112515).
• Wound healing. It is unclear if oral Lacticaseibacillus paracasei is beneficial for the treatment of SIBO. Details: Clinical research in patients with a recent episiotomy shows that taking L. paracasei (L. casei 431) 1.5 billion colony-forming units daily for 14 days modestly improves wound severity, including redness, swelling, and discharge, 5 and 15 days after birth when compared with taking placebo. There was no effect on wound pain (112519). More evidence is needed to rate Lacticaseibacillus paracasei for these uses.

(Read more about LACTICASEIBACILLUS PARACASEI)

POSSIBLY EFFECTIVE

• Antibiotic-associated diarrhea. Oral Lacticaseibacillus rhamnosus GG seems to reduce the risk of antibiotic-associated diarrhea (AAD) in adults and children. Details: Meta-analyses of clinical research show that taking L. rhamnosus GG (Culturelle) can reduce the risk of AAD in adults and children (4371,4372,7306,8511,14334,90299,95348). This strain appears to reduce the risk of AAD by about 60% to 71% (14334,90299,95348,95398). Although some contradictory evidence exists (7306), a meta-analysis of clinical research shows that taking this strain is beneficial in both inpatient and outpatient populations (90299). In children, it has been used as 10-20 billion colony-forming units (CFUs) once daily or 20 billion CFUs twice daily, given throughout the conventional antimicrobial treatment period (4371,4372,8511,14334). In adults, it has been used as 6-40 billion CFUs daily (14334,95348). However, some research suggests that this strain may only be effective in children, not adults (95389). The effect of L. rhamnosus has also been examined in combination with other products. A meta-analysis of 5 clinical trials in hospitalized or outpatient adults shows that taking L. rhamnosus, usually in combination with other probiotic strains, reduces the risk of AAD by 29% when compared with taking placebo (107635). A number of combination products containing L. rhamnosus have demonstrated benefit for preventing AAD, including L. rhamnosus CLR2, Lactobacillus acidophilus CL1285, and Lacticaseibacillus casei LBC80R (Bio-K+ Cl1285) 100 billion CFUs daily (95402,95403,25494); L. rhamnosus R0011 7.6 billion CFUs and Lactobacillus helveticus R0052 0.4 billion CFUs daily (Lacidofil STRONG, Lallemand Health Solutions) (96891); and Bifidobacterium bifidum NIZO 3804, Bifidobacterium animalis subsp. lactis NIZO 3680, Enterococcus faecium NIZO 3886, L. acidophilus NIZO 3678 and NIZO 3887, Lacticaseibacillus paracasei NIZO 3672, Lactiplantibacillus plantarum NIZO 3684, L. rhamnosus NIZO 3689, and Ligilactobacillus salivarius NIZO 3675 (Ecologic AAD) (95405). However, some combination products containing L. rhamnosus have not demonstrated benefit with respect to AAD prevention. In older adults in long-term care, taking a combination of L. rhamnosus and Bifidobacterium animalis subsp. lactis (BB-12) daily does not reduce the incidence or number of days with AAD over a 12-month period when compared with placebo (103425). In a small clinical trial in children aged 5 months to 16 years, taking a combination of L. rhamnosus KL53A, L. plantarum PL02, and Bifidobacterium longum PL03 twice daily during antibiotic treatment does not reduce the rate of AAD when compared with placebo. However, there was a modest reduction in the number of stools each day (107553). An additional large clinical trial in children aged 3 months and up shows that taking L. rhamnosus in combination with other probiotics does not reduce the risk of antibiotic-associated diarrhea when compared with taking placebo, when the more stringent definition is considered excluding diarrhea of other etiologies. However, the risk of diarrhea of any etiology is reduced by 35%. The probiotic supplement provided a total of 10 billion CFUs of L. rhamnosus W71, Lactobacillus acidophilus W37, Lactobacillus acidophilus W55, Lacticaseibacillus paracasei W20, Lactiplantibacillus plantarum W62, Ligilactobacillus salivarius W24, Bifidobacterium bifidum W23, and Bifidobacterium animalis subsp. lactis W51 daily from the first day of antibiotic treatment until 7 days after treatment ended (110969).
• Atopic dermatitis (eczema). Oral live Lacticaseibacillus rhamnosus, alone or in combination with other probiotics, seems to be beneficial for the treatment of atopic dermatitis in infants and children. It also seems to be beneficial for preventing atopic dermatitis when taken by the infant after exposure during pregnancy, but it is unclear if taking L. rhamnosus only during pregnancy or lactation is beneficial for preventing atopic dermatitis. Details: A meta-analysis of the available clinical research shows that various species of lactobacilli reduce the severity of atopic dermatitis in infants and children up to 36 months of age. Children with moderate to severe disease seem to obtain greater benefit from supplementation than those with mild disease (98436). One specific strain has shown benefit. Clinical research in infants shows that taking L. rhamnosus GG in extensively hydrolyzed whey formula providing approximately 30 billion colony-forming units (CFUs) per kg daily modestly reduces symptom severity when compared with taking placebo (107528). Other clinical research in children ages 6-36 months shows that taking L. rhamnosus GG 10 billion CFUs daily for 12 weeks more than doubles the proportion of patients with a clinically important reduction in severity when compared with taking placebo. These benefits lasted for at least 4 weeks post-supplementation. The number of days without rescue medication was reduced by about 3 days (112491). Some clinical research also shows that L. rhamnosus GG (Culturelle) might be beneficial for reducing symptoms of atopic dermatitis in infants who are allergic to cow's milk (4369). L. rhamnosus has also been shown to have beneficial effects when used in combination with other probiotics. Examples include a specific mixture (Latopic, Biomed S.A.) providing 1 billion CFUs of L. rhamnosus ŁOCK 0900 25%, L. rhamnosus ŁOCK 0908 25%, and Lacticaseibacillus casei ŁOCK 0919 50% for 3 months in children under 2 years of age (107510), and a combination of lyophilized L. rhamnosus 19070-2 and Limosilactobacillus reuteri DSM 122460 as 10 billion CFUs of each strain twice daily for 6 weeks in children aged 1-13 years (12773). Heat-killed L. rhamnosus has also been evaluated. In children aged 1-12 years with moderate atopic dermatitis, taking heat-killed L. rhamnosus IDCC 3201 (RHT3201) 10 billion CFUs daily for 12 weeks modestly reduces overall symptom severity when compared with placebo. However, these benefits were not shown in the intention to treat analysis. Also, the use of topical corticosteroids was not reduced (107527). Limited research has also evaluated oral L. rhamnosus for the treatment of atopic dermatitis in adults. One clinical study shows that taking 1 billion CFUs each of L. rhamnosus LRH020, Lactiplantbacillus plantarum PBS067, and L. reuteri PBS072 for 56 days modestly reduces the severity of symptoms and improves skin smoothness and moisturization for up to an additional 28 days when compared with placebo (107506). Other research has investigated the effects of L. rhamnosus for the PREVENTION of atopic dermatitis. A meta-analysis of clinical research shows that perinatal use of L. rhamnosus alone or in combination with other probiotics reduces the incidence of atopic dermatitis by up to 40% in children up to 2 years of age or 6-7 years of age. However, this benefit did not occur in children ages 4-5 years or 10-11 years. In these studies, L. rhamnosus was used prenatally and then possibly postnatally during lactation and/or supplemented to the newborn (112494). The reason for the age-related discrepancy is unclear; however, the number of studies investigating the effect of L. rhamnosus in children over 2 years of age was small. When lactobacilli-based probiotics are used during gestation and then supplemented to the newborn during the first 2-24 months of life, additional meta-analyses of clinical research show that this reduces the risk of the child developing atopic dermatitis by up to 40%. Most of the studies included in these analysis used L. rhamnosus GG or HN001 alone or in combination with other probiotics (90247,107503). Regimens used in some clinical research include L. rhamnosus HN001 as 6 billion CFUs daily from 35 weeks' gestation until 6 months after delivery in adults or 6 billion CFUs daily from birth to 2 years old (90603), L. rhamnosus HN001 starting at 14 weeks' gestation and continuing until 6 months postpartum (98437), as well as combinations of L. rhamnosus and Bifidobacterium animalis subsp. Lactis 1 billion CFUs daily for 6 months (102286), L. rhamnosus LPR and Bifidobacterium longum BL999 (90285), and L. rhamnosus GG, Lactobacillus acidophilus La-5, and Bifidobacterium animalis subsp. Lactis BB-12 in fermented milk starting at 36 weeks' gestation and continuing until 3 months' postpartum (96893). Some research has investigated differences between the various perinatal dosing schedules. Subgroup analyses of clinical research show that the incidence of atopic dermatitis is reduced by 48% and 34% in infants receiving L. rhamnosus prenatally and then during lactation OR via direct supplementation, respectively. However, the incidence of atopic dermatitis was not reduced in infants receiving L. rhamnosus prenatally and then during lactation AND via direct supplementation (112494). The reason for this discrepancy is unclear but may be related to the different forms of supplementation, levels found in the body, and/or the age of the child at diagnosis (98437,112494).
• Atopic disease. Taking oral Lacticaseibacillus rhamnosus GG during pregnancy and when breastfeeding, or giving it to the infant, seems to prevent atopic disease in infants and children. Details: Clinical research shows that L. rhamnosus GG (Culturelle), 10-20 billion colony-forming units (CFUs) daily taken orally 2-4 weeks before delivery and continued for the first 3-6 months of breastfeeding, prevents atopic disease (e.g., asthma, allergic rhinitis, and eczema) in infants with a family history of atopy. It appears to be equally effective when taken while breastfeeding or when taken by the bottle-feeding infant (7743,8515,11381). For the bottle-feeding infant, L. rhamnosus GG was given as 10-20 billion CFUs daily in formula (Nutramigen LGG, Mead Johnson Nutrition) for the first 3-36 months of life (7743,8515). The preventive effect of this strain in at-risk infants appears to extend up to 7 years of age (11381,99791). Other research shows that L. rhamnosus HN001, 6 billion CFUs daily taken from 35 weeks' gestation and then continued in the infant until 2 years of age, reduces the risk of atopic dermatitis by 43% and rhinoconjunctivitis by 62% when compared with placebo at 4 years of age (90603). These preventive effects appear to extend up to 11 years of age (99791). Clinical research in infants with cow's milk allergy also shows that adding L. rhamnosus GG to a hydrolyzed casein infant formula (Nutramigen LGG, Mead Johnson Nutrition) reduces the overall occurrence of other allergic manifestations when compared with casein infant formula alone. Approximately 4 infants need to take this supplemented formula in order to prevent one allergic manifestation, such as eczema, rash, asthma, and runny nose or eyes. The tolerance to cow's milk allergy is also improved over the next 3 years (96889). However, not all strains or methods of administration appear to be beneficial. Intake of L. rhamnosus HN001 only during gestation and postpartum, without supplementation in the infant, does not reduce the infant's risk of developing atopic manifestations by 12 months of age when compared with placebo. This strain was not detected in breastmilk and did not alter breastmilk protein or cytokine concentrations, which might explain these disparate findings (98437).

POSSIBLY INEFFECTIVE

• Critical illness (trauma). Enteral Lacticaseibacillus rhamnosus does not seem to be beneficial for patients with critical illness. Details: A large clinical trial in critically ill patients on mechanical ventilation shows that giving L. rhamnosus GG 10 billion colony-forming units (CFUs) enterally twice daily for a median of 9 days and up to 60 days does not reduce the risk of developing ICU-acquired infections or diarrhea or alter mortality or length of stay when compared with placebo. Also, in 15 patients, L. rhamnosus GG was isolated from sterile sites, including the blood, peritoneal or pleural fluid, hepatic or intra-abdominal abscess, or urine. Death occurred in two cases (107499).
• Peanut allergy. Oral Lacticaseibacillus rhamnosus does not seem to be beneficial for increasing the efficacy of peanut oral immunotherapy in children. Details: Clinical research in children aged 1-10 years with peanut allergy shows that taking L. rhamnosus ATCC 53103 20 billion colony-forming units (CFUs) daily for 18 months does not increase the efficacy of peanut oral immunotherapy in inducing desensitization or maintenance of sustained unresponsiveness to peanuts over the next 8 weeks. Taking L. rhamnosus decreased the number of gastrointestinal and respiratory adverse events; however, hypersensitivity and urticaria occurred more frequently in children aged 6-10 years taking L. rhamnosus (107525).
• Ventilator-associated pneumonia (VAP). Most research shows that enteral Lacticaseibacillus rhamnosus does not prevent VAP and might increase the risk of L. rhamnosus infection. Details: A large clinical trial in critically ill patients on mechanical ventilation shows that giving L. rhamnosus GG 10 billion colony-forming units (CFUs) enterally twice daily for a median of 9 days and up to 60 days does not reduce the risk of developing VAP when compared with placebo. Also, in 15 patients, L. rhamnosus GG was isolated from sterile sites, including the blood, peritoneal or pleural fluid, hepatic or intra-abdominal abscess, or urine. Death occurred in two cases (107499). In contrast, a small clinical study in critically ill patients suggests that administering L. rhamnosus GG (Culturelle) 2 billion CFUs twice daily might reduce the incidence of VAP to 19%, compared with 40% in the placebo group. In this study, half of the dose was given onto the oropharynx and half via a nasogastric tube (17116).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Abdominal pain. It is unclear if oral Lacticaseibacillus rhamnosus is beneficial for abdominal pain. Details: A meta-analysis of clinical research in children 4-18 years old with functional abdominal pain shows that taking L. rhamnosus GG does not reduce abdominal pain when compared with placebo (105130).
• Age-related cognitive decline. It is unclear if oral Lacticaseibacillus rhamnosus is beneficial for age-related cognitive decline. Details: In healthy middle-aged and older adults, clinical research shows that taking L. rhamnosus GG (Culturelle) 10 billion colony-forming units daily for 3 months does not improve cognitive function when compared with placebo. However, there was some benefit in a sub-group of individuals with cognitive impairment (105134).
• Allergic rhinitis (hay fever). Oral Lacticaseibacillus rhamnosus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research shows that drinking 250 mL of fermented milk containing L. rhamnosus GG 50 billion colony-forming units (CFUs), Lactobacillus acidophilus La-5 5 billion CFUs, and Bifidobacterium animalis subsp. lactis BB-12 50 billion CFUs from 36 weeks' gestation until 3 months postpartum does not reduce the incidence of allergic rhinitis in the child at 6 years of age when compared with placebo milk (96893).
• Attention deficit-hyperactivity disorder (ADHD). Although there has been interest in using oral Lacticaseibacillus rhamnosus for ADHD prevention or treatment, there is insufficient reliable information about the clinical effects of L. rhamnosus for this purpose.
• Bacterial vaginosis. Oral and vaginal Lacticaseibacillus rhamnosus have only been evaluated in combination with other ingredients; their effect when used alone is unclear. Details: A clinical trial shows that using vaginal capsules (EcoVag Vaginal Capsules, Bifodan A/S) containing L. rhamnosus and Lactobacillus gasseri, 100 million to 1 billion colony-forming units (CFUs) of each strain per capsule, following conventional treatment for 10 days in three subsequent menstrual cycles, increases the time from cure to relapse when compared with placebo. However, cure rates were not significantly improved in the first month of treatment (16745). Oral L. rhamnosus has also been evaluated. The available clinical research has investigated the use of a specific strain, GR-1 in combination with Limosilactobacillus reuteri RC-14. Some research suggests that this combination does not modify vaginal or fecal microbiota or improve cure or recurrence rates in patients also treated with metronidazole vaginally, when compared with taking placebo (111996,111998). Doses in these studies included at least 1 billion CFUs daily of L. rhamnosus plus L. reuteri for 30 days in otherwise healthy premenopausal adults (111996) or 2 billion CFUs of L. rhamnosus and L. reuteri twice daily for 6 months in patients with HIV (111998). However, other clinical research in patients with bacterial vaginosis suggests that taking this combination of probiotics might be beneficial for improving cure rates and improving the vaginal microbiota. In these studies, cure rates increased from 40%-50% with placebo to approximately 88% with the L. rhamnosus and L. reuteri combination. In addition to a single dose of tinidazole 2 grams or metronidazole treatment, 2 billion CFUs each of L. rhamnosus and L. reuteri were used daily for about 1 month in these studies (111997,112508). The reasons for these discrepancies are unclear but may be related to the differences in patient populations, geographical locations, and/or dosing of the product. The effect of L. rhamnosus GR-1 and L. reuteri RC-14 for the prevention of bacterial vaginosis has also been investigated. One clinical study shows that taking capsules containing 2.5 billion CFUs of this combination daily from 9-14 weeks' gestation until delivery does not affect the rate of bacterial vaginosis when compared with placebo (102292). In patients with HIV treated with metronidazole 400 mg twice daily for 10 days, taking 2 billion CFUs of L. rhamnosus and L. reuteri twice daily for 6 months does not improve the recurrence rates when compared with taking placebo (111998).
• Bipolar disorder. Oral Lacticaseibacillus rhamnosus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study shows that taking at least 100 million colony-forming units of a combination of L. rhamnosus GG and Bifidobacterium animalis subsp. lactis BB-12 for 24 weeks after discharge from the hospital for mania reduces the time to first rehospitalization when compared with placebo. The hazard ratio for the first rehospitalization due to worsening of psychiatric symptoms was 0.37 for the combination probiotic group when compared with placebo. Among patients who were re-hospitalized, taking the combination probiotic reduced the mean duration of rehospitalization by 5.4 days when compared with placebo (96896).
• Cancer. Although there has been interest in using oral Lacticaseibacillus rhamnosus for cancer prevention or treatment, there is insufficient reliable information about the clinical effects of L. rhamnosus for this condition.
• Canker sores. It is unclear if oral Lacticaseibacillus rhamnosus is beneficial for canker sore prevention or treatment. Details: A systematic review and meta-analysis of mainly small and preliminary clinical trials shows that oral lactobacilli have a small effect on pain from canker sores. However, only two studies in the analysis used L. rhamnosus. One individual study shows that taking L. rhamnosus Lcr35 1.5 billion colony-forming units (CFUs) daily for 3 months has no effect on the number of canker sores. Another small study shows that taking a combination of L. rhamnosus, Lacticaseibacillus paracasei, Lactobacillus acidophilus, and Bifidobacterium animalis subsp. lactis reduces pain, but does not affect the number of lesions or healing time, when compared with placebo (105146). The individual studies were small and may have been underpowered to detect a difference between groups.
• Chemotherapy-induced diarrhea. It is unclear if oral Lacticaseibacillus rhamnosus is beneficial for preventing chemotherapy-induced diarrhea. Details: Preliminary clinical research in patients with colorectal cancer receiving chemotherapy with 5-fluorouracil shows that taking L. rhamnosus GG (Culturelle) 10-20 billion colony-forming units (CFUs) daily in two divided doses orally during 24 weeks of chemotherapy, with or without guar gum, reduces severe diarrhea, abdominal discomfort, and the number of chemotherapy dose reductions required when compared with not taking L. rhamnosus GG (16736).
• Child development. Oral Lacticaseibacillus rhamnosus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: An 11-year follow-up study shows that taking L. rhamnosus and Bifidobacterium animalis subsp. lactis daily from 35 weeks' gestation until birth, or for six months after birth if breastfeeding, followed by supplementation of the child until two years of age, does not affect neurocognitive outcomes such as attention, intelligence, executive function, depression, and anxiety, when compared with placebo (102287).
• Clostridioides difficile infection. It is unclear if oral Lacticaseibacillus rhamnosus is beneficial for the prevention of C. difficile infection. Details: Observational research has found that providing a specific combination (Bio-K+ 50 Billion; Bio-K Plus International) of L. rhamnosus CLR2, Lactobacillus acidophilus CL1285, and Lacticaseibacillus casei LBC80R, as 50-100 billion colony-forming units (CFUs) daily for 5 days to patients who are on antibiotics for at least 2 days reduces the hospital-wide incidence of C. difficile by approximately 40%. The incidence rate was decreased by at least 50% in the highest risk individuals taking this combination (107529). Conversely, individual clinical studies included in some meta-analyses suggest that L. rhamnosus is not effective for the primary prevention of C. difficile infections; however, the number of patients with C. difficile in the individual studies is likely too small for an adequate comparison (14334,90231). Current guidelines from the Infectious Diseases Society of America (IDSA) state that there is insufficient information to recommend administration of probiotics for the primary prevention of C. difficile-associated diarrhea (107538). While some preliminary clinical research shows that taking L. rhamnosus GG might reduce the risk of C. difficile diarrhea recurrence (4392,4394), meta-analyses of more recent, higher-quality clinical data show that this strain is not effective for this purpose (14334,18088,90934,95368,95370).
• Cognitive function. It is unclear if oral Lacticaseibacillus rhamnosus improves cognitive function in young adults. Details: A small clinical trial shows that taking L. rhamnosus JB-1 as 1 billion colony-forming units daily for 4 weeks does not improve cognitive function when compared with placebo in healthy young adults (105148).
• Cognitive impairment. It is unclear if oral Lacticaseibacillus rhamnosus is beneficial for cognitive impairment. Details: In middle-aged and older adults with cognitive impairment, a small clinical trial shows that taking L. rhamnosus GG (Culturelle) 10 billion colony-forming units daily for 3 months results in an improved cognitive function score when compared with placebo (105134).
• Colic. It is unclear if oral Lacticaseibacillus rhamnosus is beneficial for colic. Details: A small clinical trial in exclusively breastfed infants with colic shows that taking L. rhamnosus ATCC 53103 5 billion colony-forming units (CFUs) daily for 28 days reduces full-force crying time by a median of 135 minutes when compared with taking placebo (112000). Other clinical research in infants aged 4-12 weeks with colic shows that taking a combination of L. rhamnosus and Limosilactobacillus reuteri (FloraActive) 250 million CFUs with fructo-oligosaccharides 3.33 mg and vitamin D3 200 IU daily for 28 days reduces mean crying time by 2.7 hours by the end of the study, compared to a 1.9-hour reduction in the vitamin D group (99783). However, another small clinical study in infants shows that taking L. rhamnosus GG 10 billion CFUs with inulin 225 mg daily starting within 4 days of birth does not prevent colic symptoms or diagnosis at 4 months when compared with inulin alone (112497). This study was a secondary analysis of a trial designed to investigate the effect of L. rhamnosus on atopic disease prevention.
• Common cold. Although there has been interest in using oral Lacticaseibacillus rhamnosus for preventing the common cold, there is insufficient reliable information about the clinical effects of L. rhamnosus for this condition.
• Constipation. It is unclear if oral Lacticaseibacillus rhamnosus is beneficial for constipation. Details: A small clinical study in children less than 5 years old with functional constipation shows that taking L. rhamnosus Lcr35 800 million CFUs twice daily for 4 weeks does not improve stool frequency when compared with placebo (95340). However, a small clinical trial shows that taking a combination of L. rhamnosus IDCC 3201, Lactiplantibacillus plantarum IDCC 3501, Lacticaseibacillus casei IDCC 3451, Bifidobacterium animalis subsp. lactis IDCC 4301, Bifidobacterium breve IDCC 4401, Lactococcus lactis IDCC 2301, xylooligosaccharide, and dietary fiber as nondigestible maltodextrin, oat fiber, and psyllium husk fiber (ID-HWS1000) modestly increases stool frequency and improves symptoms of functional constipation in adults when compared with placebo (107517). It is unclear if these effects are due to L. rhamnosus, other ingredients, or the combination.
• Coronavirus disease 2019 (COVID-19). Although there has been interest in using oral Lacticaseibacillus rhamnosus for reducing symptoms of COVID-19, there is insufficient reliable information about the clinical effects of L. rhamnosus for this condition.
• Crohn disease. It is unclear if oral Lacticaseibacillus rhamnosus is beneficial for preventing Crohn disease recurrence. Details: A small clinical trial in adults shows that taking L. rhamnosus GG (Culturelle) 6 billion colony-forming units (CFUs) twice daily for one year does not prevent recurrence of Crohn disease after surgery (12767). Another small clinical trial in children and young adults shows that taking L. rhamnosus 10 billion CFUs twice daily for up to two years in addition to standard therapy does not prolong remission when compared with placebo (107539).
• Cystic fibrosis. It is unclear if oral Lacticaseibacillus rhamnosus is beneficial for cystic fibrosis. Details: Clinical research in children aged 2-16 years with cystic fibrosis shows that taking L. rhamnosus GG 6 billion colony-forming units (CFUs) daily for 12 months does not reduce the odds of having at least one pulmonary exacerbation, the odds of hospitalization over 12 months, or the total number of exacerbations or hospitalizations when compared with placebo (107570).
• Dental caries. It is unclear if oral Lacticaseibacillus rhamnosus is beneficial for dental caries prevention. Details: A large clinical trial in children aged 1-6 years shows that providing milk containing L. rhamnosus GG ATCC 53103 (Gefilus, Valio Ltd., Riihimaki Dairy) five days a week for 7 months does not reduce the overall odds of developing dental caries when compared with placebo. However, there was a 44% reduction in caries odds when caries risk was taken into consideration. The milk provided at least 500,000 colony-forming units (CFUs) per mL, with each child consuming 42-584 mL daily (107571). However, a meta-analysis of this and other large clinical trials in preschool children shows that taking L. rhamnosus in juice or milk modestly reduces the incidence of dental caries and prevents tooth decay progression when compared with taking placebo (112507). The effect of L. rhamnosus added to milk has also been investigated in adults. Clinical research in middle-aged and older adults with at least two primary root caries lesions shows that taking L. rhamnosus LB21 200 million CFUs in milk, either alone or with added fluoride 5 ppm, once daily for 15 months modestly reduces lesion severity when compared with placebo milk. However, the milk containing L. rhamnosus in the absence of fluoride was less effective than either the combination or the milk containing fluoride only (107573). The validity of this study is limited by a dropout rate of 38%.
• Dental plaque. Oral Lacticaseibacillus rhamnosus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in adolescent males aged 13-15 years with mild to moderate gingival inflammation shows that taking two lozenges containing L. rhamnosus GG (Probiotical SpA) and Bifidobacterium animalis subsp. lactis BB-12 (Chr. Hansen A/S) twice daily for 4 weeks does not reduce plaque when compared with placebo. However, here was a benefit on levels of some salivary and plaque pathogenic bacteria. Each lozenge provided L. rhamnosus 440 million colony-forming units (CFUs) plus B. animalis subsp. lactis BB-12 480 million CFUs (107574). A small clinical trial in healthy adults shows that taking four lozenges daily providing a total daily dose of 2 billion CFUs each of L. rhamnosus GG ATCC 53103 (Probiotical SpA) and B. animalis subsp. lactis BB-12 DSM 15954 (Chr. Hansen A/S) for 4 weeks modestly reduces plaque and gingivitis when compared with placebo (107572). Another small clinical trial in adults with moderate gingival inflammation shows that taking a tablet providing 50 million CFUs each of L. rhamnosus PB01 DSM 14869 and Latilactobacillus curvatus EB10 DSM 32307 twice daily after brushing for 4 weeks does not improve plaque or bleeding during probing when compared with placebo (107575).
• Denture stomatitis. Although there has been interest in using oral Lacticaseibacillus rhamnosus for denture stomatitis, there is insufficient reliable information about the clinical effects of L. rhamnosus for this condition.
• Diabetes. It is unclear if oral Lacticaseibacillus rhamnosus is beneficial for treatment of type 1 or type 2 diabetes. Oral L. rhamnosus is unlikely to be beneficial for the prevention of gestational diabetes and may actually increase the risk for other complications. Details: One small clinical study in patients with type 2 diabetes shows that taking a specific combination product (Familact probiotics, ZistTakhmir Co.) containing L. rhamnosus and other probiotic bacteria daily for 6 weeks does not reduce fasting blood glucose or plasma insulin when compared with placebo. This product contains L. rhamnosus 1.5 billion colony-forming units (CFUs), Lactobacillus acidophilus 2 billion CFUs, Lacticaseibacillus casei 7 billion CFUs, Lactobacillus delbrueckii subsp. bulgaricus 200 million CFUs, Bifidobacterium breve 30 billion CFUs, Bifidobacterium longum 7 billion CFUs, and Streptococcus thermophilus 1.5 billion CFUs (99790). A meta-analysis of clinical research shows that taking lactobacilli, usually L. rhamnosus, during pregnancy is unlikely to PREVENT gestational diabetes and increases the relative risk of pre-eclampsia by 85% when compared with placebo (105185). Studies have used L. rhamnosus HN001 6 billion CFUs daily from 14-16 weeks' gestation to 24-30 weeks' gestation (96888), L. rhamnosus GG and Bifidobacterium animalis subsp. lactis (BB-12) at least 1 billion CFUs daily from 16-20 weeks' gestation until 28 weeks' gestation, or L. rhamnosus HN001 ATCC SD5675 and B. animalis subsp. lactis 420 DSM 22089 (Dupont Nutrition & Health) 10 billion CFUs each daily throughout pregnancy, with or without fish oil (102284,105144). Limited evidence has also assessed the effects of L. rhamnosus for type 2 diabetes. Taking L. rhamnosus 10 billion CFUs, L. acidophilus 1 billion CFUs, and Bacillus coagulans GanedenBC30 (GBI-30, 6086) 100 billion CFUs with fructo-oligosaccharides 500 mg daily for 12 weeks modestly reduces fasting blood glucose and insulin and improves measures of insulin resistance when compared with placebo (107536). Some research has also assessed the effects of L. rhamnosus in combination with other probiotics in children 8-17 years old with new onset type 1 diabetes. One clinical study shows that taking L. rhamnosus GG ATCC 53103 and Bifidobacterium animalis subsp. lactis Bb12 DSM 15954 1 billion CFUs daily for 6 months does not reduce insulin requirements or glycated hemoglobin over 12 months when compared with placebo. Additionally, C-peptide levels and the maintenance of residual pancreatic beta-cell function were not affected when compared with placebo (107518).
• Diarrhea. It is unclear if oral Lacticaseibacillus rhamnosus is beneficial for the prevention or treatment of acute diarrhea. Details: L. rhamnosus GG (e.g., Culturelle) 6 billion CFUs twice daily, given prophylactically at hospital admission, seems to reduce the risk of non-rotaviral diarrhea in infants and children ages 1-36 months (7741). Furthermore, giving 37 billion CFUs of this strain daily, 6 days weekly for 15 months, can reduce the occurrence of diarrhea from all causes in undernourished children aged 6-24 months (4373). However, in older adults in long-term care, taking a combination of L. rhamnosus and Bifidobacterium animalis subsp. lactis (BB-12) 13-16 billion CFUs daily does not reduce the incidence or duration of diarrhea over a 12-month period when compared with placebo (103425). A small clinical study in children with dysentery being treated with ceftriaxone shows that taking a specific combination probiotic sachet (Kidilact, Zisttakhmir Company) containing L. rhamnosus, Lacticaseibacillus casei, Lactobacillus acidophilus, Lactobacillus delbrueckii subsp. bulgaricus, Bifidobacterium infantis, Bifidobacterium breve, and Streptococcus thermophilus daily for 5 days modestly reduces the duration of diarrhea, hospitalization, and blood in diarrhea when compared with control (102417). L. rhamnosus has yielded inconsistent results in the treatment of acute gastroenteritis, which is defined as three or more episodes of watery stools per day, with or without vomiting, for fewer than 3-7 days. While the European Society for Pediatric Infectious Diseases recommends probiotics in hospitalized children with diarrhea (98469) and the Infectious Disease Society of America (IDSA) recommends probiotics for the outpatient treatment of acute diarrhea (95388), both guidelines note that most evidence is low quality. Furthermore, these guidelines were published prior to the completion of the recent high-quality studies showing no benefit with L. rhamnosus GG, alone or in combination with Lactobacillus helveticus (98427,98428,103441,110925). These studies in children 3 months to 4 years of age with acute gastroenteritis show that taking either L. rhamnosus GG (e.g., Culturelle) 1 billion CFUs or a combination product containing L. rhamnosus GG 3.8 billion CFUs and L. helveticus 200 million CFUs twice daily for 5 days does not reduce the risk of a moderate to severe episode of acute gastroenteritis in the 14-28 days after starting the probiotic when compared with placebo (98427,98428,103441,110925). These products also did not reduce the incidence or severity of diarrhea or vomiting, the number of unexpected healthcare visits (98427,98428,103441,110925), the number of day care days missed, or the rate of household transmission (98427) when compared with placebo, regardless of the causative pathogen. Additional clinical research shows that treatment with L. rhamnosus GG 1 billion CFUs twice daily for 5 days does not reduce the severity or duration of diarrhea in otherwise healthy children 6 months to 6 years of age (90280).
• Gingivitis. Oral Lacticaseibacillus rhamnosus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in adolescent males aged 13-15 years with mild to moderate gingival inflammation shows that taking two lozenges containing L. rhamnosus GG (Probiotical SpA) and Bifidobacterium animalis subsp. lactis BB-12 (Chr. Hansen A/S) twice daily for 4 weeks modestly reduces gingivitis when compared with placebo. Each lozenge provided L. rhamnosus 440 million colony-forming units (CFUs) plus B. animalis subsp. lactis BB-12 480 million CFUs (107574). A small clinical trial in healthy adults shows that taking four lozenges daily providing a total daily dose of 2 billion CFUs each of L. rhamnosus GG ATCC 53103 (Probiotical SpA) and B. animalis subsp. lactis BB-12 DSM 15954 (Chr. Hansen A/S) for 4 weeks modestly reduces plaque and gingivitis when compared with placebo (107572). However, a small clinical trial in adults with moderate gingival inflammation shows that taking a tablet providing 50 million CFUs each of L. rhamnosus PB01 DSM 14869 and Latilactobacillus curvatus EB10 DSM 32307 twice daily after brushing for 4 weeks does not improve plaque or bleeding with probing when compared with placebo (107575).
• Group B streptococcal colonization. Oral Lacticaseibacillus rhamnosus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A meta-analysis of two clinical trials shows that taking L. rhamnosus GR-1 and Limosilactobacillus reuteri RC-14, starting at 35-37 weeks' gestation and continuing until delivery, does not improve GBS clearance during pregnancy. However, a well-designed study included in this analysis shows that taking 4 billion CFUs daily more than doubles the number of patients testing negative for GBS at delivery (105165). In addition, a small clinical trial shows that taking this combination as 2.5 billion colony-forming units (CFUs) each daily for 12 weeks, starting at weeks 23-25 of gestation, does not prevent the rate of GBS vaginal/rectal colonization at 35-37 weeks' gestation (107567).
• Helicobacter pylori. It is unclear if oral Lacticaseibacillus rhamnosus in combination with standard therapies for H. pylori can improve eradication rates or reduce the risk of adverse effects; the available research is conflicting. Details: Most clinical research in adults has shown that L. rhamnosus does not improve H. pylori eradication rates when used in combination with Lactobacillus acidophilus, Bifidobacterium bifidum, and Streptococcus faecium and taken with triple therapy consisting of furazolidone, tetracycline, and lansoprazole (90279), when used in combination with six other probiotics species and taken with bismuth quadruple therapy (90291), or when L. rhamnosus GG is used with triple therapy consisting of rabeprazole, clarithromycin, and tinidazole (12763). However, a large, more recent study shows that taking L. rhamnosus GG in combination with Bifidobacterium animalis subsp. lactic BB-12 (Normia, JGL; Christian Hanssen) twice daily for 14 days with triple therapy results in eradication in 87% of patients, compared with 73% of those taking triple therapy and placebo (107514). L. rhamnosus has also been evaluated for reducing the risk of adverse effects from H. pylori treatment. In two studies in which L. rhamnosus is taken along with other probiotics, the rate of adverse effects is not reduced when compared with placebo (90279,90291). However, when L. rhamnosus GG is used alone, or in combination with Bifidobacterium animalis subsp. lactis BB-12, triple therapy-related adverse effects are modestly reduced when compared with placebo (12763,107514). There was no longer a difference in adverse events between probiotic therapy and placebo during the 2-4 weeks of follow up (12763).
• HIV/AIDS. Although there has been interest in using oral Lacticaseibacillus rhamnosus for HIV/AIDS, there is insufficient reliable information about the clinical effects of L. rhamnosus for this condition.
• Hypercholesterolemia. Although there has been interest in using oral Lacticaseibacillus rhamnosus for hypercholesterolemia, there is insufficient reliable information about the clinical effects of L. rhamnosus for this condition.
• Hypertension. Although there has been interest in using oral Lacticaseibacillus rhamnosus for hypertension, there is insufficient reliable information about the clinical effects of L. rhamnosus for this condition.
• Irritable bowel syndrome (IBS). It is unclear if oral Lacticaseibacillus rhamnosus is beneficial for IBS; the available research is conflicting. Details: A meta-analysis of clinical research shows that L. rhamnosus reduces abdominal pain, but does not improve the frequency of pain relief, in patients with IBS (107594). In contrast, a small clinical trial shows that taking L. rhamnosus GG 10 billion CFUs daily for 8 weeks does not improve symptoms of IBS (12771). L. rhamnosus has also been evaluated in combination with other probiotics. Clinical research shows that taking a product (Duolac Care) containing L. rhamnosus, Bifidobacterium animalis susbp. lactis, Bifidobacterium breve, Lactobacillus acidophilus, Lactiplantibacillus plantarum, and Streptococcus thermophilus twice daily for 4 weeks can relieve symptoms in 72% of patients with IBS (95353). A clinical study in patients with diarrhea-predominant IBS (IBS-D) shows that taking a specific multi-species probiotic (NordBiotic, MBM Biotix) containing L. rhamnosus LR110, L. acidophilus LA120, L. plantarum LP140, Lacticaseibacillus paracasei LPC100, Lacticaseibacillus casei LC130, B. breve BB010, Bifidobacterium longum BL020, Bifidobacterium bifidum BF030, Bifidobacterium animalis subsp. lactis BL040, and Streptococcus thermophilus ST250 as 2.5 billion CFUs total twice daily for 8 weeks improves overall symptom severity, as well as pain severity, pain frequency, and quality of life, when compared with placebo. Symptom severity was rated as mild by approximately 60% of those taking the probiotic mixture, compared with 30% of those taking placebo (107516). However, other clinical research shows that taking a combination of L. rhamnosus CLR2, L. acidophilus CL1285, and L. casei LBC80R 50 billion CFUs each daily for 3 months does not improve symptoms of IBS in the whole study population, although it may have some benefit in specific sub-groups (99789).
• Lactose intolerance. It is unclear if oral Lacticaseibacillus rhamnosus is beneficial for lactose intolerance. Details: In patients with persistent symptoms related to lactose intolerance despite a lactose-free diet, a small clinical trial shows that taking a combination product (Zircombi) containing L. rhamnosus HN001 1 billion CFUs, Bifidobacterium longum BB536 4 billion CFUs, and vitamin B6 1.4 mg daily for 30 days modestly improves symptoms of bloating and constipation, but not abdominal pain, when compared with placebo (105153).
• Malnourishment-related diarrhea. Oral Lacticaseibacillus rhamnosus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in children aged 6 months to 4 years of age hospitalized with severe acute malnutrition shows that taking L. rhamnosus LGG and Bifidobacterium lactis BB-12 5 billion colony-forming units each daily during hospitalization and for 8-12 weeks as an outpatient does not affect diarrhea incidence or severity or the number of days with diarrhea during hospitalization. However, the number of days with diarrhea as an outpatient was reduced by 2.2 days (110996).
• Malnutrition. Oral Lacticaseibacillus rhamnosus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in children aged 6 months to 4 years of age hospitalized with severe acute malnutrition shows that taking L. rhamnosus LGG and Bifidobacterium lactis BB-12 5 billion colony-forming units each daily during hospitalization and for 8-12 weeks as an outpatient does not affect pneumonia incidence, duration, or severity, weight gain, duration of hospitalization, or other outcomes (110996).
• Metabolic syndrome. Although there has been interest in using oral Lacticaseibacillus rhamnosus for metabolic syndrome, there is insufficient reliable information about the clinical effects of L. rhamnosus for this condition.
• Necrotizing enterocolitis (NEC). It is unclear if oral Lacticaseibacillus rhamnosus is beneficial or safe for NEC prevention. Details: Most meta-analyses of clinical research show that giving lactobacilli enterally reduces the risk of NEC and/or severe NEC in preterm, mainly very low birth weight (VLBW), infants. Some meta-analyses support the use of lactobacilli in combination with bifidobacteria, as opposed to lactobacilli alone for reducing the risk of NEC (95344,95351,103437,103445,104157,105162,105164). However, research on the use of L. rhamnosus, specifically, is limited. Large retrospective reports suggest that taking L. rhamnosus GG does not significantly reduce the risk of NEC in preterm, VLBW infants. The most recent report suggests that the use of L. rhamnosus is associated with an almost 2-fold increased incidence of NEC when compared with not using L. rhamnosus (17121,112501). Also, guidance among regulatory agencies and clinical organizations varies with respect to the use of probiotics in very low birth weight infants under 1000 grams. The US Food and Drug Administration (FDA) warns that preterm infants given probiotics are at risk of serious infections caused by the bacteria or fungi contained in probiotics due to cases reported in this group of infants (111610). Also, The American Academy of Pediatrics does not support the routine administration of probiotics to preterm infants, particularly those with a birth weight below 1000 grams, due to conflicting data on safety and efficacy and potential for harm in this vulnerable population (111608). The Canadian Paediatric Society, the American Gastroenterological Association, and the European Society for Paediatric Gastroenterology, Hepatology and Nutrition state that probiotic combinations may be of benefit in reducing the incidence of NEC in preterm neonates over 1000 grams. However, L. rhamnosus is not specifically recommended (103003,111609,111611).
• Neurogenic bladder. Although there has been interest in using intravesical Lacticaseibacillus rhamnosus for reducing urinary symptoms associated with neurogenic bladder, there is insufficient reliable information about the clinical effects of L. rhamnosus for this purpose.
• Nonalcoholic fatty liver disease (NAFLD). Oral Lacticaseibacillus rhamnosus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: In children with NAFLD, clinical research shows that taking a specific combination product (Prokid, Gostaresh Milad Pouya Company) containing L. rhamnosus DSMZ 21690 2 billion colony-forming units (CFUs), Lactobacillus acidophilus ATCC B3208 3 billion CFUs, Bifidobacterium animalis subsp. lactis DSMZ 32269 6 billion CFUs, and Bifidobacterium bifidum ATCC SD6576 2 billion CFUs daily for 12 weeks normalizes liver sonography findings in 53% of children, compared with 17% of those taking placebo. In addition, levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are reduced by 30% and 25%, respectively. There was no effect on body mass index or blood lipids when compared with placebo (105156).
• Obesity. It is unclear if oral Lacticaseibacillus rhamnosus is beneficial for weight loss. Details: Clinical research in adults with obesity shows that taking L. rhamnosus 162 million colony-forming units (CFUs) twice daily for 24 weeks does not reduce body weight or fat mass when compared with placebo. However, when only females are considered, L. rhamnosus seems to reduce body weight by an additional 1.8 kg when compared with placebo (90289). Another clinical trial shows that taking 10 billion CFUs each of L. rhamnosus HN001 and Bifidobacterium animalis subsp. lactis 420 daily during pregnancy and for 6 months postpartum, alone or with 2 capsules daily of fish oil (Croda Europe Ltd.), reduces the odds of the infant being overweight at 24 months by at least 78% when compared with taking placebo (110336). It is unclear if this effect is related to L. rhamnosus, B. lactis, or their combination.
• Oropharyngeal candidiasis. Although there has been interest in using oral Lacticaseibacillus rhamnosus for oropharyngeal candidiasis, there is insufficient reliable information about the clinical effects of L. rhamnosus for this condition.
• Osteoarthritis. Although there has been interest in using oral Lacticaseibacillus rhamnosus for osteoarthritis, there is insufficient reliable information about the clinical effects of L. rhamnosus for this condition.
• Otitis media. It is unclear if oral Lacticaseibacillus rhamnosus is beneficial for preventing otitis media in children. Details: Preliminary clinical research in children aged 1-6 years who attend daycare shows that taking milk containing L. rhamnosus GG (Culturelle) does not reduce the incidence of otitis media infections when compared with placebo (8565).
• Periodontitis. It is unclear if oral Lacticaseibacillus rhamnosus is beneficial for periodontitis. Details: A meta-analysis of 2 small clinical trials in patients with periodontitis shows that using oral L. rhamnosus as an adjunctive therapy to scaling and root planing does not improve clinical attachment or reduce probing pocket depth when compared with control (107622). Similarly, a small clinical trial in patients with stage III periodontitis following scaling and root planing shows that taking L. rhamnosus SP1 (Macrofood S.A.) as 20 million colony-forming units (CFUs) daily for 3 months does not improve plaque, probing pocket depth, bleeding on probing, or clinical attachment, when compared with placebo (107576). However, all studies were small and might not have been adequately powered to detect differences between groups.
• Polycystic ovary syndrome (PCOS). It is unclear if oral Lacticaseibacillus rhamnosus is beneficial for PCOS. Details: A small clinical trial in overweight or obese patients with PCOS who are consuming an energy-restricted diet shows that taking L. rhamnosus 12 billion colony-forming units (CFUs) daily for 20 weeks does not increase weight loss or have beneficial effects on blood lipid levels when compared with placebo (107577). However, this study was small and may not have been adequately powered to detect a difference between groups. Another clinical trial shows that 31.3% of patients with PCOS taking L. rhamnosus in combination with other probiotics daily for 6 months had regular menstrual cycles compared with 12.5% of those taking placebo. There were also modest improvements in testosterone levels and waist circumference, but not other hormones, insulin resistance, body weight, or most measures of quality of life. The product provided L. rhamnosus UBLR-58 2 billion CFUs along with Bifidobacterium bifidum UBBB-55, Lactobacillus acidophilus UBLA-34, Lactiplantibacillus plantarum UBLP-40, Lacticaseibacillus casei UBLC-42, Limosilactobacillus fermentum UBLF-31, Limosilactobacillus reuteri UBLRu-87, and fructo-oligosaccharides (FOS) daily for 2 months and then twice daily for 4 months. All patients also underwent dietary and lifestyle changes (110974). It is unclear if any benefits are due to L. rhamnosus, the other probiotics, or their combination.
• Postoperative bowel function. It is unclear if oral Lacticaseibacillus rhamnosus is beneficial for improving postoperative bowel function. Details: A small preliminary clinical trial shows that taking L. rhamnosus GG (Dicoflor 60, Vitis pharma, Warsaw, Poland) 6 million colony-forming units twice daily for 30 days following major pancreatic surgery reduces the time to first passing gas and stool, by about 1.1 and 2 days, respectively, when compared with receiving standard nutrition only (112495).
• Postoperative infection. It is unclear if oral Lacticaseibacillus rhamnosus is beneficial for preventing postoperative infections. Details: A small preliminary clinical trial shows that taking L. rhamnosus GG (Dicoflor 60, Vitis pharma, Warsaw, Poland) 6 million colony-forming units twice daily for 30 days following major pancreatic surgery does not reduce the incidence of postoperative infections when compared with receiving standard nutrition only (112495).
• Postoperative recovery. It is unclear if oral Lacticaseibacillus rhamnosus is beneficial for improving postoperative recovery. Details: A small preliminary clinical trial shows that taking L. rhamnosus GG (Dicoflor 60, Vitis pharma, Warsaw, Poland) 6 million colony-forming units twice daily for 30 days following major pancreatic surgery reduces the length of hospital stay by 2 days when compared with receiving standard nutrition only (112495).
• Postpartum depression. It is unclear if oral Lacticaseibacillus rhamnosus is beneficial for postpartum depression. Details: Clinical research shows that taking L. rhamnosus HN001 6 billion colony-forming units (CFUs) daily from 14-16 weeks' gestation does not reduce the rate of clinically significant depression when compared with placebo. However, taking this product modestly reduces feelings of postpartum depression and anxiety, and 47% fewer patients experienced clinically significant anxiety between 1-2 months' postpartum when compared with placebo (107541). Other clinical research shows that taking a combination of L. rhamnosus HN001 ATCC SD5675 and Bifidobacterium animalis subsp. lactis 420 DSM 22,089 (Dupont Nutrition & Health) 10 billion CFUs daily, alone or with fish oil providing eicosapentaenoic acid (EPA) 0.44 grams and docosahexaenoic acid (DHA) 3.8 grams daily, does not reduce symptoms of postpartum depression or anxiety when compared with placebo. Supplements were started in the second trimester of pregnancy and continued until 6 months after delivery (107496).
• Pouchitis. Although there has been interest in using oral Lacticaseibacillus rhamnosus for pouchitis, there is insufficient reliable information about the clinical effects of L. rhamnosus for this condition.
• Respiratory tract infections. It is unclear if oral Lacticaseibacillus rhamnosus is beneficial for respiratory tract infections; the available research is conflicting. Details: The evidence related to the use of L. rhamnosus for respiratory tract infections is mixed. A meta-analysis of clinical research shows that administering L. rhamnosus GG to infants and children reduces the risk of upper respiratory tract infections (URTIs) by about 38%. However, this analysis shows that giving this strain to infants and children does not reduce the risk of overall respiratory infections or the risk of lower respiratory tract infections (95347). Also, the evidence from individual clinical trials is mixed. One large clinical trial shows that children ages 1-6 years who attend daycare centers get fewer and less severe respiratory infections when given approximately 260 mL milk daily containing L. rhamnosus GG (Culturelle) 0.5-1 million colony-forming units (CFUs) per mL (8565). However, other clinical research in infants aged 6 to 12 months shows that taking L. rhamnosus HN001 one million colony-forming units (CFUs) per gram of follow-on formula daily for 12 weeks does not reduce the incidence of confirmed or parentally reported upper respiratory tract infections when compared with formula without added probiotics. Infants consumed an average of 141 grams of formula daily (110988). Also, a large clinical trial in children aged 2-6 years shows that taking L. rhamnosus GG 1 billion CFUs daily for 16 weeks does not reduce the incidence of physician-diagnosed URTIs when compared with taking placebo. There was also no difference in the number of children, days, or days absent with a URTI (112492). L. rhamnosus has also been investigated in combination with other probiotics. In college students, clinical research shows that taking L. rhamnosus GG and Bifidobacterium lactis BB-12 one billion CFUs each daily for 12 weeks reduces the duration of upper respiratory tract infection by about 2 days when compared with placebo. Symptom severity was reduced by 34%. There was also a small reduction in the number of missed school days, but not work days (110993). Conversely, in older adults in long-term care, taking a combination of L. rhamnosus and Bifidobacterium animalis subsp. lactis (BB-12) 13-16 billion CFUs daily does not reduce the incidence of upper or lower respiratory tract infections when compared with placebo over a 12-month period, and actually increases the use of antibiotics for lower respiratory tract infections by 2.2 days (103425).
• Rheumatoid arthritis (RA). It is unclear if oral Lacticaseibacillus rhamnosus is beneficial for RA. Details: A small clinical trial in patients with RA shows that taking L. rhamnosus GG ATCC 53103 (Gefilus, Valio Ltd.) 10 billion colony-forming units (CFUs) twice daily for 12 months does not reduce symptoms when compared with placebo (107533). An additional small clinical trial shows that taking a total of 2 billion colony-forming units (CFUs) daily of a combination of L. rhamnosus GR-1 and Limosilactobacillus reuteri RC-14 (Chr Hansen) for 14 weeks does not improve symptom severity when compared with placebo (107569). Both studies were small and may not have been adequately powered to detect differences between groups.
• Rotaviral diarrhea. It is unclear if oral Lacticaseibacillus rhamnosus is beneficial for rotaviral diarrhea. Details: Some meta-analyses of clinical research and several small clinical trials show that L. rhamnosus GG (Culturelle) can reduce the duration of diarrhea in infants and children with rotavirus infection (1253,4369,4377,8568,112504). These studies were conducted prior to the availability of the rotavirus vaccine. Conversely, large, high-quality studies conducted after the introduction of the rotavirus vaccine do not show benefits (98427,98428,112504). Clinical research in children 3 months to 4 years of age with acute gastroenteritis, including rotaviral gastroenteritis, shows that taking either L. rhamnosus GG (Culturelle) or a combination product containing L. rhamnosus GG 3.8 billion CFUs and Lactobacillus helveticus 200 million CFUs twice daily for 5 days does not reduce the risk of a moderate to severe episode of acute gastroenteritis in the 14 days after starting the probiotic when compared with placebo (98427,98428,110925). Taking these probiotic products also does not reduce the incidence or severity of diarrhea or vomiting, the number of unexpected healthcare visits (98427,98428,110925), the number of daycare days missed, the rate of household transmission (98427), or the pathogen load (103441) when compared with placebo. Approximately 48% to 65% of the children enrolled in these studies were vaccinated against rotavirus, but it is not clear if this altered the study outcomes (98427,98428,103441). More research is needed to evaluate the effect of lactobacillus in the treatment of rotaviral diarrhea in children who have not been vaccinated against rotavirus. Although L. rhamnosus GG and other species have shown modest benefit in preliminary clinical studies in children who have not received the rotavirus vaccine, the evidence is conflicting, and not all of the evaluated patients had confirmed rotavirus infection (102295). The current guidelines related to the treatment of viral diarrhea are also conflicting. While the World Gastroenterology Organization has not made a recommendation (98471), the European Society for Pediatric Infectious Diseases recommends probiotics in hospitalized children with diarrhea (98469) and the Infectious Disease Society of America (IDSA) recommends probiotics for the outpatient treatment of acute diarrhea (95388). However, these guidelines note that most evidence is low quality and is not specific to rotavirus infection. Furthermore, these guidelines were released prior to the publication of the most recent, high-quality studies showing no benefit with the use of L. rhamnosus (98427,98428). Recent guidelines by the American Gastroenterology Association conditionally recommend against the use of probiotics for the treatment of acute infectious gastroenteritis in children (103003).
• Short bowel syndrome. Although there has been interest in using oral Lacticaseibacillus rhamnosus for short bowel syndrome, there is insufficient reliable information about the clinical effects of L. rhamnosus for this condition.
• Small intestinal bacterial overgrowth (SIBO). Although there has been interest in using oral Lacticaseibacillus rhamnosus for SIBO, there is insufficient reliable information about the clinical effects of L. rhamnosus for this condition.
• Stress. It is unclear if oral Lacticaseibacillus rhamnosus GG is beneficial for stress. Details: Preliminary clinical research in university students shows that taking L. rhamnosus HN001 6 billion colony-forming units (CFUs) daily for 8-13 weeks during the semester does not reduce stress or anxiety during exams when compared with taking placebo (112496).
• Travelers' diarrhea. It is unclear if oral Lacticaseibacillus rhamnosus GG is beneficial for the prevention of travelers' diarrhea; the available research is conflicting. Details: Clinical research shows that taking L. rhamnosus GG (Culturelle) 2 billion colony-forming units daily orally, starting two days prior to a trip and continuing until the end of the trip, seems to reduce the occurrence of diarrhea in child and adult travelers (4374,10216). However, a meta-analysis which included two small clinical studies evaluating the use of L. rhamnosus GG in adults traveling to different parts of the world found no benefit for the prevention of travelers' diarrhea when compared with placebo (101445). The effectiveness of this strain can vary significantly based upon the destination of travel. Destinations in the same country can have different results, probably due to differences in bacteria and other microorganisms at different locations (10216).
• Ulcerative colitis. Although there has been interest in using oral Lacticaseibacillus rhamnosus for ulcerative colitis, there is insufficient reliable information about the clinical effects of L. rhamnosus for this condition.
• Urinary tract infections (UTIs). It is unclear if oral or intravaginal Lacticaseibacillus rhamnosus is beneficial for the prevention or treatment of UTIs. Details: Some small clinical studies show that intravaginal use of L. rhamnosus might provide modest benefit for preventing UTI (6094,6095). These trials used suppositories containing 0.5 gram (1.6 billion colony-forming units (CFUs)) of L. rhamnosus and Limosilactobacillus fermentum twice weekly for 2 weeks, then once a month for 2 months (6095) or a vaginal solution containing L. rhamnosus 100 billion viable bacteria/mL in a dose of 1 mL twice weekly (6094). However, some research indicates that L. rhamnosus is ineffective in establishing vaginal colonization, regardless of the route of administration (90257). This may explain why studies which have evaluated the use of L. rhamnosus as a single agent for this indication have failed to show benefit (4581). Oral L. rhamnosus has also been evaluated for the prevention of UTI recurrence. Clinical research in postmenopausal adults shows that an oral combination of L. rhamnosus GR-1 and Limosilactobacillus reuteri RC-14, standardized to at least 1 billion CFUs and taken twice daily for 12 months, demonstrates similar efficacy to trimethoprim/sulfamethoxazole 480 mg once daily for reducing the number of symptomatic UTIs. Although this combination was not associated with the increase in antimicrobial resistance that occurred with the use of antibiotic prophylaxis, the antibiotic delayed the median time to first recurrence by two-fold and reduced the number of confirmed microbiological infections when compared with lactobacillus (90235). In children aged 4 months to 5 years with a previous UTI, clinical research shows that taking a specific combination (Complete Probiotic Platinum) of L. rhamnosus, Lactobacillus acidophilus, Bifidobacterium bifidum, and Bifidobacterium animalis subsp. lactis for 18 months increases the median time to the first incidence of recurrence by approximately 3 months and increases the percentage of children without a UTI during the study period from 83% to 97% (103436). However, in older adults in long-term care, taking a combination of L. rhamnosus and Bifidobacterium animalis subsp. lactis (BB-12) 13-16 billion CFUs daily does not reduce the incidence of UTI when compared with placebo over a 12-month period (103425).
• Vaginal candidiasis. It is unclear if oral or intravaginal Lacticaseibacillus rhamnosus is beneficial for the prevention or treatment of vaginal candidiasis. Details: A combination of L. rhamnosus and Bifidobacterium longum (Lactobac) given orally, or a combination of L. rhamnosus, Lactobacillus delbrueckii, Lactobacillus acidophilus, and Streptococcus thermophilus (Femilac) given intravaginally, does not seem to reduce the risk of vaginal candidiasis infection following use of antibiotics (12108). However, there is preliminary evidence that individuals with candidiasis who use intravaginal suppositories containing 1 billion colony-forming units of L. rhamnosus GG twice daily for 7 days in combination with conventional treatment might have subjective improvement in symptoms (4397). More evidence is needed to rate Lacticaseibacillus rhamnosus for these uses.

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INSUFFICIENT RELIABLE EVIDENCE to RATE

• Antibiotic-associated diarrhea. Oral Ligilactobacillus salivarius has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A large clinical trial in children aged 3 months and up shows that taking L. salivarius in combination with other probiotics does not reduce the risk of antibiotic-associated diarrhea when compared with taking placebo, when the more stringent definition is considered excluding diarrhea of other etiologies. However, the risk of diarrhea of any etiology is reduced by 35%. The probiotic supplement provided a total of 10 billion colony-forming units (CFUs) of L. salivarius W24, Bifidobacterium bifidum W23, Bifidobacterium animalis subsp. lactis W51, Lactobacillus acidophilus W37, L. acidophilus W55, Lacticaseibacillus paracasei W20, Lactiplantibacillus plantarum W62, and Lacticaseibacillus rhamnosus W71, daily from the first day of antibiotic treatment until 7 days after treatment ended (110969). A small clinical trial in patients taking amoxycillin shows that taking a specific product (Ecologic AAD) for 14 days modestly reduces diarrhea-like bowel movements, defined as a frequency of at least 3 per day and/or a very soft or watery consistency, when compared with taking placebo. The product used in this study provides a total of 5 billion CFUs twice daily of L. salivarius NIZO 3675, Lactobacillus acidophilus NIZO 3678 and NIZO 3887, Lacticaseibacillus paracasei NIZO 3672, Lactiplantibacillus plantarum NIZO 3684, Lacticaseibacillus rhamnosus NIZO 3689, Bifidobacterium bifidum NIZO 3804, Bifidobacterium animalis subsp. lactis NIZO 3680, and Enterococcus faecium NIZO 3886 (95405).
• Asthma. Oral Ligilactobacillus salivarius has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A large clinical trial in children ages 3-14 years with asthma shows that taking a combination of L. salivarius LS01 (DSM 22775) and Bifidobacterium breve B632 (DSM 24706) one billion colony-forming units (CFUs) each twice daily for 8 weeks and then once daily for 8 weeks modestly reduces the number of asthma exacerbations. The odds of having one or two asthma exacerbations was more than three fold in children taking placebo when compared with children taking probiotics. There was no effect on the duration of exacerbation or use of corticosteroids (111004).
• Atopic dermatitis (eczema). It is unclear if oral Ligilactobacillus salivarius is beneficial for atopic dermatitis. Details: L. salivarius LS01 (DSM 2275) has been investigated for the treatment of atopic dermatitis in adults. A small clinical trial shows that taking L. salivarius LS01 1 billion colony-forming units (CFUs) twice daily for 16 weeks modestly reduces symptom severity and improves skin-related quality of life when compared to baseline. However, it is unclear if L. salivarius is beneficial when compared with taking placebo (112541). Another small clinical trial shows that taking a preparation containing L. salivarius LS01 5 billion CFUs daily, along with Streptococcus thermophilus ST10 and tara gum, daily for 1 month modestly improves symptoms when compared with taking placebo (112544). It is unclear if this effect is due to L. salivarius, other ingredients, or the combination. L. salivarius has also been investigated in children with atopic dermatitis. In children up to 11 years of age, a small clinical trial shows that taking L. salivarius LS01 (DSM 22775) daily reduces symptom severity and itch intensity when compared with baseline. Benefits persisted for 4 weeks after treatment. Children took 2 billion CFUs daily for 8 weeks followed by 1 billion CFUs daily for an additional 8 weeks (112540). However, it is unclear if these changes are due to the product or natural changes of the condition. Other clinical research has investigated the effects of L. salivarius in combination with other probiotics for the prevention of atopic dermatitis. A combination of L. salivarius, Lacticaseibacillus paracasei, Bifidobacterium animalis subsp. lactis, and Bifidobacterium bifidum, a total of 10 billion CFUs daily provided from 36 weeks' gestation and then to the infant until age 6 months, reduces the prevalence of atopic dermatitis at age two by approximately 60% (90234). It is unclear if this effect is due to L. salivarius, other ingredients, or the combination.
• Bacterial vaginosis. Vaginal Ligilactobacillus salivarius has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A preliminary clinical trial shows that vaginal application with a tablet providing at least one billion CFUs of a combination of L. salivarius, Lactiplantibacillus plantarum, and Levilactobacillus brevis (Florisia) might be beneficial for the treatment of bacterial vaginosis. Using this combination for 8 days reduces the proportion of patients with bacterial vaginosis by about 79% when compared to baseline. Taking this product does not seem to be more beneficial than using a pH lowering vaginal product (110951).
• Dental caries. It is unclear if oral heat-killed or viable Ligilactobacillus salivarius is beneficial for preventing dental caries. Details: Preliminary clinical research in children ages 3-6 years shows that chewing tablets containing heat-killed L. salivarius (HM6 Paradens) (Acidolac Dentifix Kids, Polpharma, Poland) 10 mg twice daily for 2 weeks reduces the prevalence and incidence of dental caries over 12 months by an intermediate to large amount when compared with usual care with toothbrushing twice daily (112538).
• Diabetes. It is unclear if oral Ligilactobacillus salivarius is beneficial for gestational diabetes. Details: Clinical research in patients with newly diagnosed gestational diabetes or impaired glucose tolerance at less than 34 weeks gestation shows that taking L. salivarius UCC118 1 billion colony-forming units daily until delivery does not affect levels of fasting glucose, the need for pharmacological therapy, or birthweight of the infant, when compared with taking placebo. There were also no clinically relevant benefits on plasma lipid levels. All patients were given dietary advice and regular follow-up care (96894).
• Exercise-induced respiratory infections. It is unclear if oral Ligilactobacillus salivarius is beneficial for preventing exercise-induced respiratory infections. Details: A small clinical trial in athletes shows that taking L. salivarius 20 billion colony-forming units daily for 16 weeks during spring endurance training does not reduce the proportion of patients developing upper respiratory tract symptoms for at least a week or the number of episodes, when compared with taking placebo (112542). However, the study may have been inadequately powered to detect a difference between groups.
• Halitosis. It is unclear if oral Ligilactobacillus salivarius is beneficial for halitosis. Details: A small clinical trial shows that taking a dissolving tablet containing L. salivarius WB21 (Wakamoto Pharmaceutical, Japan) 670 million colony-forming units (CFUs) and xylitol 3 times daily for 2 weeks reduces the concentration of volatile sulfur compounds, but does not reduce halitosis or tongue coating, when compared with taking placebo (112551). Also, another small clinical trial shows that chewing a dissolving gum containing L. salivarius G60 1 billion CFUs with inulin 1 gram every 12 hours after meals for 10 days, but not L. salivarius alone, modestly reduces halitosis and improves quality of life when compared with taking placebo. There was no effect on tongue coating (112548). However, these studies may have been inadequately powered to detect a difference between the L. salivarius alone and placebo groups. In contrast, one small and preliminary clinical trial shows that taking a dissolving tablet containing L. salivarius WB21 (Wakamoto Pharmaceutical, Japan) 670 million CFUs and xylitol 3 times daily modestly reduces oral malodor when compared to baseline. L. salivarius was taken by patients with physiologic or pathological halitosis for 2 or 4 weeks, respectively (112549). The validity of this study is limited by the lack of a comparator group.
• Irritable bowel syndrome (IBS). Although there has been interest in using oral Ligilactobacillus salivarius for IBS, there is insufficient reliable information about the clinical effects of L. salivarius for this condition.
• Mastitis. It is unclear if oral Ligilactobacillus salivarius is beneficial for mastitis prevention or treatment. Details: A small clinical study shows that taking L. salivarius PS2 1 billion colony-forming units (CFUs) daily from 27-32 weeks' gestation until childbirth reduces mastitis rate by 56% when compared with placebo in patients with a history of infectious mastitis. Milk bacterial counts and breast pain in patients that did develop mastitis were also modestly reduced (102291). L. salivarius has also been investigated in the treatment of infectious mastitis. Taking L. salivarius CECT5713 1 billion CFUs daily for 3 weeks results in breast pain recovery and mastitis recurrence in 85% and 7.1% of patients, respectively, compared with 29% and 30.7% of those taking an antibiotic. Milk bacterial counts were also reduced in patients taking L. salivarius (112524). The validity of this study is limited by the lack of blinding. Also, the type of antibiotic used was dependent on the primary care provider.
• Otitis media. It is unclear if oral Ligilactobacillus salivarius is beneficial for otitis media prevention. Details: A small and preliminary clinical trial in children with recurrent otitis media shows that taking L. salivarius PS7 1 billion colony-forming units daily for 6 months reduces the number of acute otitis media episodes by 84% when compared to the 6-month period prior to supplementation (112545). The validity of this study is limited by the lack of a direct comparator group and the use of historical data as comparison.
• Periodontitis. It is unclear if oral Ligilactobacillus salivarius is beneficial for periodontitis. Details: Small clinical trials in patients with mild to moderate periodontitis show that taking L. salivarius does not affect plaque severity, pocket depth, or bleeding on probing when compared with taking placebo (112537,112550). However, there seems to be a modest benefit in some parameters in smokers (112550). These studies have used a tablet providing L. salivarius WB21 (Wakamate Ds, Wakamoto Pharmaceutical Co., Japan) 670 million CFUs 3 times daily for 8 weeks (112550) or a suspension providing an unknown quantity of L. salivarius SGL03 (Salistat SGL03) daily for 30 days (112537). This product (Salistat SGL03) also provided unknown quantities of gluco-oligosaccharides, lactoferrin, essential oils of lemon and rosemary, and vitamin D.
• Pregnancy-induced nausea and vomiting. Oral Ligilactobacillus salivarius has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small preliminary clinical trial shows that taking probiotics during pregnancy reduces the severity and duration of nausea and vomiting by 16% to 54%. There was also a small benefit on stool hardness. A specific probiotic (Probiotics 10, Nature's Bounty) was taken as 2 capsules daily for two back-to-back cycles of six days with probiotics and two days without. Each capsule contained a total of 10 billion colony-forming units of L. salivarius Ls-33, Lactobacillus acidophilus La-14, Lactiplantibacillus plantarum 299v and DSM 15312, Lactobacillus delbrueckii subsp. bulgaricus Lb-87, Lacticaseibacillus paracasei DSM 13434 and Lpc-37, Levilactobacillus brevis Lbr-35, Lacticaseibacillus casei Lc-11, and Bifidobacterium animalis subsp. lactis Bl-04, along with inulin 200 mg (107199).
• Ulcerative colitis. Oral Ligilactobacillus salivarius has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in patients with moderate to severe symptoms taking mesalazine 1200 mg daily shows that taking an unknown dose of L. salivarius twice daily along with Bifidobacterium bifidum BGN4 and Lactobacillus acidophilus (Acronelle, Bromatech srl, Milan, Italy) for 2 years modestly improves patient- and physician-scales of overall symptoms when compared with taking mesalazine alone. There were also improvements in stool frequency and rectal bleeding (110981). More evidence is needed to rate Ligilactobacillus salivarius for these uses.

(Read more about LIGILACTOBACILLUS SALIVARIUS)

LIKELY SAFE ...when used orally and appropriately. Bifidobacterium lactis has been safely used alone or in combination with other probiotics in clinical trials lasting up to 12 weeks (92255,98502,105158,107572,107581,107586,110979,110985,110986,110992)(110993,110998,110999).

CHILDREN: LIKELY SAFE
when used orally and appropriately in children of most ages. Bifidobacterium lactis has been safely used alone or in combination with other probiotics in infants and children for up to 15 months (3169,3458,92265,95381,95382,98736,105149,107582,107583,107585)(107587,107590,110984,110987,110988,110991,110994,110995). A combination probiotic containing B. lactis and Lactobacillus acidophilus (HOWARU Protect, Danisco) has been used safely for up to 6 months in children aged 3-5 years (16847). A specific combination of B. lactis, Bifidobacterium bifidum, and L. acidophilus (Complete Probiotic Platinum) has also been used safely for up to 18 months in children aged 4 months to 5 years (103436). In addition, in children ages 4-17 years, 1 billion CFUs of a 1:1:1 combination of B. lactis CECT 8145, Lacticasebacillus casei CECT 9104, and Bifidobacterium longum CECT 7347 has been used safely for 12 weeks (107531). There is insufficient reliable information available about the safety of B. lactis in preterm infants with a birth weight under 1000 grams. Cases of bacteremia have occurred rarely in preterm infants given other probiotics (102416,111610,111612,111613,111850,111852,111853). The US Food and Drug Administration (FDA) has issued a warning about cases of serious infections caused by probiotics reported in very preterm or very low birth weight infants under 1000 grams (111610). Similarly, the American Academy of Pediatrics does not support the routine administration of probiotics to these infants due to conflicting data on safety and efficacy (111608).

PREGNANCY AND LACTATION:
Insufficient reliable information available. A meta-analysis of four clinical trials shows that taking probiotics during pregnancy increases the relative risk of pre-eclampsia by 85% when compared with placebo. Although the specific effects of Bifidobacterium lactis are unclear from this analysis, three of the included studies used B. lactis in combination with Lacticaseibacillus rhamnosus (105185). More information is needed to determine if certain patients are at increased risk.

(Read more about BIFIDOBACTERIUM ANIMALIS SUBSP. LACTIS)

LIKELY SAFE ...when used orally and appropriately. Bifidobacterium breve has been safely used alone or in combination with other probiotics in clinical trials lasting up to one year (3261,6087,11379,12769,12775,14338,14370,14371,103447,111002)(111003,111005).

CHILDREN: LIKELY SAFE
when used orally and appropriately in children of most ages. Bifidobacterium breve has been safely used alone or in combination with other probiotics in infants and children for up to 12 months (17726,35377,92256,103449,105150,105151,107497,107598,111001)(111004,111008,111015). Cases of bacteremia have occurred rarely in children (107597). There is insufficient reliable information available about the safety of B. breve in preterm infants with a birth weight under 1000 grams. Cases of bacteremia have occurred rarely in preterm infants given B. breve or other probiotics (102416,111610,111612,111613,111850,111852,111853). The US Food and Drug Administration (FDA) has issued a warning about cases of serious infections caused by probiotics reported in very preterm or very low birth weight infants under 1000 grams (111610). Similarly, the American Academy of Pediatrics does not support the routine administration of probiotics to these infants due to conflicting data on safety and efficacy (111608).

PREGNANCY AND LACTATION:
There is insufficient reliable information available about the safety of Bifidobacterium breve during pregnancy or lactation. However, there are currently no reasons to expect safety concerns when used appropriately.

(Read more about BIFIDOBACTERIUM BREVE)

LIKELY SAFE ...when used orally and appropriately. Bifidobacterium longum has been safely used alone or in combination with other probiotics in clinical trials lasting up to one year (1233,12108,13054,14334,35382,35403,35424,103440,103446,105129)(107593,110968,110972,111773,111776,111847,111851,111854,111857,111858).

CHILDREN: LIKELY SAFE
when used orally and appropriately in children of most ages. Bifidobacterium longum has been safely used alone or in combination with other probiotics in infants and children for up to 4 months (3162,35377,35383,35393,35406,35407,92266,98736,107531,110924)(110976,111001,111015,111825,111833,111848). There is insufficient reliable information available about the safety of B. longum in preterm infants with a birth weight under 1000 grams. Cases of bacteremia have occurred rarely in preterm infants given these and other probiotics (102416,111610,111612,111613,111850,111852,111853). The US Food and Drug Administration (FDA) has issued a warning about cases of serious infections caused by probiotics reported in very preterm or very low birth weight infants under 1000 grams (111610). Similarly, the American Academy of Pediatrics does not support the routine administration of probiotics to these infants due to conflicting data on safety and efficacy (111608).

PREGNANCY AND LACTATION: POSSIBLY SAFE
when used orally and appropriately, short-term. A combination of Bifidobacterium longum and Lacticaseibacillus rhamnosus has been used with apparent safety throughout pregnancy (105128,105144). A combination of B. longum BB536 and Bifidobacterium breve M-16V has been used with apparent safety from about 4 weeks before the expected due date until delivery (111015). Also, a combination of B. longum and Lacticaseibacillus paracasei has been used with apparent safety from 2 months prior to delivery until 2 months after delivery during lactation (90285).

(Read more about BIFIDOBACTERIUM LONGUM)

LIKELY SAFE ...when used orally and appropriately. Lacticaseibacillus casei has been safely used alone or in combination with other ingredients in studies lasting up to 8 weeks (90230,112517).

CHILDREN: LIKELY SAFE
when used orally and appropriately in children of most ages. Lacticaseibacillus casei has been safely used alone in studies lasting up to 4 months (14373,107544). Also, a specific mixture (Latopic, Biomed S.A.) providing 1 billion CFUs of L. casei ŁOCK 0919 50%, Lacticaseibacillus rhamnosus ŁOCK 0900 25%, and L. rhamnosus ŁOCK 0908 25% has been used with apparent safety for 3 months in children under 2 years of age (107510). In addition, in children ages 4-17 years, a 1:1:1 combination of L. casei CECT 9104, Bifidobacterium animalis subsp. lactis CECT 8145, and Bifidobacterium longum CECT 7347 providing 1 billion CFUs has been used with apparent safety for 12 weeks (107531). There is insufficient reliable information available about the safety of L. casei in preterm infants with a birth weight under 1000 grams. Cases of bacteremia have occurred rarely in preterm infants given other probiotics (102416,111610,111612,111613,111850,111852,111853). The US Food and Drug Administration (FDA) has issued a warning about cases of serious infections caused by probiotics reported in very preterm or very low birth weight infants under 1000 grams (111610). Similarly, the American Academy of Pediatrics does not support the routine administration of probiotics to these infants due to conflicting data on safety and efficacy (111608).

PREGNANCY: POSSIBLY SAFE
when used orally and appropriately. A combination of Lacticaseibacillus casei, Lactobacillus acidophilus, and Bifidobacterium bifidum has been used with apparent safety for 6 weeks, starting at 24-28 weeks' gestation (95416,98430).

LACTATION:
There is insufficient reliable information available about the safety of Lacticaseibacillus casei during lactation. However, there are currently no reasons to expect safety concerns when used appropriately.

(Read more about LACTICASEIBACILLUS CASEI)

LIKELY SAFE ...when live or heat-killed Lacticaseibacillus paracasei are used orally and appropriately. Live L. paracasei alone or in combination with other probiotics has been safely used in studies lasting up to 4 years (6087,14370,14371,35393,35407,103440,105133,107555,107557,110979)(111937,111938,111940,111943,111948,111950,111951,111953,111954,111955)(111958,111959,112512,112513,112518,112519). Non-viable, heat-killed L. paracasei has been safely used in studies lasting up to 3 months (111939,111940,111947). There is insufficient reliable information available about the safety of live or non-viable, heat-killed L. paracasei when used topically.

CHILDREN: LIKELY SAFE
when used orally and appropriately in children of most ages. Lacticaseibacillus paracasei alone or in combination with Limosilactobacillus fermentum has been used with apparent safety for up to 3 months in children 1-18 years old (98440). Also, live or heat-killed L. paracasei LP-33 has been used with apparent safety for 30 days in children aged 5 years and older (107532). In children ages 2-12 years, a specific combination product (Visbiome, ExeGi Pharma) containing L. paracasei and seven other probiotics has been used safely for 3 months (107497). Also, L. paracasei has been used with apparent safety in combination with Lactiplantibacillus plantarum for up to 12 weeks (107556). L. paracasei DN-114 011 has been taken safely for 90 days in children ages 3-6 years in fermented milk (DanActive, Dannon) (112515). There is insufficient reliable information available about the safety of L. paracasei in preterm infants with a birth weight under 1000 grams. Cases of bacteremia have occurred rarely in preterm infants given other probiotics (102416,111610,111612,111613,111850,111852,111853). The US Food and Drug Administration (FDA) has issued a warning about cases of serious infections caused by probiotics reported in very preterm or very low birth weight infants under 1000 grams (111610). Similarly, the American Academy of Pediatrics does not support the routine administration of probiotics to these infants due to conflicting data on safety and efficacy (111608).

PREGNANCY AND LACTATION: POSSIBLY SAFE
when used orally and appropriately. A combination of Lacticaseibacillus paracasei and Bifidobacterium longum from 2 months prior to delivery until 2 months after delivery has been used with apparent safety (90285).

(Read more about LACTICASEIBACILLUS PARACASEI)

LIKELY SAFE ...when used orally and appropriately. Lacticaseibacillus rhamnosus has been safely used alone or in combination with other probiotics in studies lasting up to 6 months (4367,12108,35393,105134,107569,107572,107573,107575,107577,111793)(111996,111997,111998,112493,112496,112503,112508). ...when used intravaginally and appropriately. L. rhamnosus has been used safely in studies lasting from one week to six months (4397,12108,90283,111999). There is insufficient reliable information available about the safety of non-viable, heat-killed L. rhamnosus formulations when used orally.

CHILDREN: LIKELY SAFE
when used orally and appropriately in children of most ages. The strain Lacticaseibacillus rhamnosus GG has been used safely in studies lasting from five days to 36 months (4369,4372,4373,4377,7741,8565,8566,8567,8568,14334)(90280,96889,98427,98428,99782,107518,107539,107571,110988,112000)(112491,112492,112494,112502). L. rhamnosus LOCK 0900 has been used safely in combination with other probiotics for 3 months (107510). There is insufficient reliable information about the safety of non-viable, heat-killed L. rhamnosus formulations in children when taken orally. Also, there is insufficient reliable information available about the safety of L. rhamnosus in preterm infants with a birth weight under 1000 grams. Cases of bacteremia have occurred rarely in preterm infants given L. rhamnosus and other probiotics (102416,111610,111612,111613,111850,111852,111853). The US Food and Drug Administration (FDA) has issued a warning about cases of serious infections caused by probiotics reported in very preterm or very low birth weight infants under 1000 grams (111610). Similarly, the American Academy of Pediatrics does not support the routine administration of probiotics to these infants due to conflicting data on safety and efficacy (111608).

PREGNANCY: POSSIBLY SAFE
when used orally and appropriately. Lacticaseibacillus rhamnosus GG has been used with apparent safety starting 2-4 weeks before delivery (7743,8515). L. rhamnosus HN001 has been used from 14-16 weeks' gestation until 6 months post-delivery (96888,98437). The combination of L. rhamnosus with Bifidobacterium longum has been used from 2 months prior to delivery until 2 months after delivery or throughout pregnancy (90285,105128,105144). The combination of L. rhamnosus GR-1 and Limosilactobacillus reuteri RC-14 has been used for up to two trimesters during pregnancy (102292,107562). A combination of L. rhamnosus, Lactobacillus jensenii, Lactobacillus crispatus, and Lactobacillus gasseri has been used safely for 3-4 weeks from 32-36 weeks' gestation (105131). A meta-analysis of four clinical trials shows that taking probiotics during pregnancy increases the relative risk of pre-eclampsia by 85% when compared with placebo. Although the specific effects of L. rhamnosus are unclear from this analysis, two of the included studies used L. rhamnosus GG and one used L. rhamnosus HN001 (105185). More information is needed to determine if certain patients are at increased risk.

LACTATION: POSSIBLY SAFE
when used orally and appropriately. Lacticaseibacillus rhamnosus GG has been used with apparent safety when breastfeeding for up to six months (7743,8515) and L. rhamnosus HN001 has been used from 14-16 weeks' gestation until 6 months post-delivery (96888,98437). A combination of L. rhamnosus and Bifidobacterium longum has been used with apparent safety from 2 months prior to delivery until 2 months after delivery (90285).

(Read more about LACTICASEIBACILLUS RHAMNOSUS)

POSSIBLY SAFE ...when used orally and appropriately. Ligilactobacillus salivarius has been safely used in studies lasting up to 16 weeks (112543,112544,112548,112550). There is insufficient reliable information available about the safety of L. salivarius when used vaginally.

CHILDREN: POSSIBLY SAFE
when used orally and appropriately in children of most ages. Ligilactobacillus salivarius has been safely used alone or in combination with other probiotics in studies lasting up to 16 weeks (111004,112540). There is insufficient reliable information available about the safety of L. salivarius in preterm infants with a birth weight under 1000 grams. Cases of bacteremia have occurred rarely in preterm infants given other probiotics (102416,111610,111612,111613,111850,111852,111853). The US Food and Drug Administration (FDA) has issued a warning about cases of serious infections caused by probiotics reported in very preterm or very low birth weight infants under 1000 grams (111610). Similarly, the American Academy of Pediatrics does not support the routine administration of probiotics to these infants due to conflicting data on safety and efficacy (111608).

PREGNANCY: POSSIBLY SAFE
when used orally and appropriately. Ligilactobacillus salivarius has been safely used from about 30 weeks' gestation or diagnosis of gestational diabetes until delivery (96894,102291).

LACTATION:
There is insufficient reliable information available about the safety of Ligilactobacillus salivarius during lactation. However, there are currently no reasons to expect safety concerns when used appropriately.

(Read more about LIGILACTOBACILLUS SALIVARIUS)

ANTIBIOTIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = D Theoretically, taking Bifidobacterium lactis with antibiotic drugs might decrease the effectiveness of B. lactis.  Details Since B. lactis preparations usually contain live and active organisms, simultaneously taking antibiotics might kill a significant number of the organisms (1740,22802). Tell patients to separate administration of antibiotics and B. lactis preparations by at least 2 hours.

(Read more about BIFIDOBACTERIUM ANIMALIS SUBSP. LACTIS)

ANTIBIOTIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = D Theoretically, taking Bifidobacterium breve with antibiotic drugs might decrease the effectiveness of B. breve.  Details Since B. breve preparations usually contain live and active organisms, simultaneously taking antibiotics might kill a significant number of the organisms (1740,22802). Tell patients to separate administration of antibiotics and B. breve preparations by at least 2 hours.

(Read more about BIFIDOBACTERIUM BREVE)

ANTIBIOTIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = D Theoretically, taking Bifidobacterium longum with antibiotic drugs might decrease the effectiveness of B. longum.  Details Since B. longum preparations usually contain live and active organisms, simultaneously taking antibiotics might kill a significant number of the organisms (1740,22802). Tell patients to separate administration of antibiotics and B. longum preparations by at least 2 hours.

(Read more about BIFIDOBACTERIUM LONGUM)

ANTIBIOTIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Mild •  Occurrence = Probable •  Level of Evidence = D Theoretically, taking Lacticaseibacillus casei with antibiotic drugs might decrease the effectiveness of L. casei.  Details L. casei preparations usually contain live and active organisms. Therefore, simultaneously taking antibiotics might kill a significant number of the organisms (1740). Tell patients to separate administration of antibiotics and L. casei preparations by at least two hours.

(Read more about LACTICASEIBACILLUS CASEI)

ANTIBIOTIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Mild •  Occurrence = Probable •  Level of Evidence = D Theoretically, taking Lacticaseibacillus paracasei with antibiotic drugs might decrease the effectiveness of L. paracasei.  Details L. paracasei preparations usually contain live and active organisms. Therefore, simultaneously taking antibiotics might kill a significant number of the organisms (1740). Tell patients to separate administration of antibiotics and L. paracasei preparations by at least two hours.

(Read more about LACTICASEIBACILLUS PARACASEI)

ANTIBIOTIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Mild •  Occurrence = Probable •  Level of Evidence = D Theoretically, taking Lacticaseibacillus rhamnosus with antibiotic drugs might decrease the effectiveness of L. rhamnosus.  Details L. rhamnosus preparations usually contain live and active organisms. Therefore, simultaneously taking antibiotics might kill a significant number of the organisms (1740). Tell patients to separate administration of antibiotics and L. rhamnosus preparations by at least two hours.

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ANTIBIOTIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Mild •  Occurrence = Probable •  Level of Evidence = D Theoretically, taking Ligilactobacillus salivarius with antibiotic drugs might decrease the effectiveness of L. salivarius.  Details Ligilactobacillus salivarius preparations usually contain live and active organisms. Therefore, simultaneously taking antibiotics might kill a significant number of the organisms (1740). Tell patients to separate administration of antibiotics and L. salivarius preparations by at least two hours.

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General ...Orally, Bifidobacterium lactis seems to be well tolerated by most patients.
Most Common Adverse Effects:
Orally: Diarrhea.
Serious Adverse Effects (Rare):
Orally: There is concern that probiotics may cause infections in some people.

Dermatologic ...In clinical research, two cases of rash, one with itching, were reported by patients taking a combination of Bifidobacterium lactis BB-12, Lacticaseibacillus paracasei F19, and Lactobacillus acidophilus La5. However, it is not clear if these adverse effects were due to B. lactis, other probiotics, or the combination, or if the events were idiosyncratic (90236).

Gastrointestinal ...Bloating and flatulence have been reported with probiotic use; however, these adverse effects have not been reported from ingestion of Bifidobacterium lactis in particular. When taken orally, B. lactis can cause diarrhea and other gastrointestinal complaints in children (3169,95381,105149). Gastrointestinal complaints including worsening diarrhea, abdominal pain, constipation, stomach burn, and flatulence have been reported rarely (110986,110999).

Immunologic ...There have been cases of Bifidobacterium bacteremia in critically ill patients (102416,107599). These cases are rare and none seem to be due to Bifidobacterium lactis alone.
A specific preparation (NBL probiotic ATP, Nobel) containing B. lactis, Lacticaseibacillus casei, Lacticaseibacillus rhamnosus, Lactiplantibacillus plantarum, fructo-oligosaccharides, galacto-oligosaccharides, colostrum, and lactoferrin was found to be a significant risk factor for vancomycin-resistant Enterococcus colonization in premature infants. Although there was no direct link to determine causation, it was hypothesized that the probiotic mixture helped to mediate the acquisition and transfer of antibiotic resistance genes (96890).

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General ...Orally, Bifidobacterium breve seems to be well tolerated by most patients.
Serious Adverse Effects (Rare):
Orally: There is concern that B. breve may cause bacteremia in certain patients.

Gastrointestinal ...Bloating and flatulence have been reported with probiotic use; however, these adverse effects have not been reported from ingestion of Bifidobacterium breve in particular.

Immunologic ...There have been rare cases of Bifidobacterium bacteremia related to probiotic use in critically ill infants and adults (102416,107597,107599). In addition, cases of B. breve bacteremia have occurred in preterm infants or young children using probiotics (102416,107597). In a review of 298 term and preterm infants who were admitted to the neonatal intensive care unit of a hospital in Japan and received B. breve BBG-01 over a five-year period, bacteremia occurred in six patients (2%). Concomitant conditions included gastrointestinal perforation, food-induced enterocolitis syndrome, adhesive ileus, ileal volvulus, and aspiration pneumonia following esophageal atresia repair (107597). In one case report, B. breve BBG-01 was provided to an infant starting two days after birth and the day of surgery for an omphalocele. The infant also had bilious gastric fluid with elevated inflammatory markers. It is thought that the intestinal surgical repair might have led to the translocation of the ingested B. breve (107596).
Some cases of B. breve bacteremia do not seem to be directly related to probiotic use. There have been rare cases of B. breve bacteremia and necrotizing fasciitis in patients with type 2 diabetes. One patient had pre-existing chronic diabetic foot ulcers and the other had abscesses near the groin (111007,111011). A childhood history of frequent consumption of fermented beverages containing B. breve was thought to have resulted in B. breve in the intestinal flora of one of these patients, aged 42 years (111011). However, it is unclear if consumption of an unknown quantity of B. breve more than 20 years previously would play a role in this outcome. There is also a rare case of ventriculoperitoneal shunt B. breve infection possibly related to poor oral hygiene and dentition (111014).

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General ...Orally, Bifidobacterium longum seems to be well tolerated by most patients.
Serious Adverse Effects (Rare):
Orally: There is concern that B. longum may cause bacteremia in certain patients.

Gastrointestinal ...When taken orally, abdominal discomfort, pain, and distension have been reported rarely (111773,111847,111856). Flatulence has been reported rarely with Bifidobacterium longum when used alone or in combination with other species of probiotics (107520,111773). Other rare gastrointestinal side effects have included constipation and gastrointestinal motor disorder (111773).

Immunologic ...There have been rare cases of Bifidobacterium bacteremia in critically ill infant and adult patients (102416,107599). Various cases of Bifidobacterium longum bacteremia, sometimes presenting as sepsis, have occurred in preterm infants using probiotics (102416,111610,111612,111850,111852,111853). In one case report, a 15-month-old female infant with congenital heart defects and recent surgery to replace a mechanical heart valve developed Bifidobacterium sepsis after being treated with IV antibiotics, extracorporeal membrane oxygenation (ECMO), and oral probiotics containing B. longum. It was thought that ECMO contributed to translocation of bifidobacteria from the gut and into the blood (102416). In 5 cases, very-low birthweight preterm infants developed B. longum bacteremia following the use of a specific probiotic product providing B. longum and Lactobacillus acidophilus (Infloran) for the prevention of necrotizing enterocolitis; antibiotic treatment was required in at least some of the cases (111850,111852,111853). Cases of sepsis related to B. longum have also occurred in adults; however, association with supplementation is unlikely. In one case, sepsis with B. longum occurred following acupuncture. This was likely due to needle contamination and not to supplementation (1236). In another case, a 71-year-old male with liver cirrhosis and prostate cancer developed B. longum lumbar vertebrodiscitis. The source was thought to be translocation from the intestine (111859). A 42-year-old male developed B. longum peritonitis secondary to intestinal perforation (111855).

Pulmonary/Respiratory ...When taken orally, a dry cough has been reported by a single patient in a clinical trial (111851).

Other ...When taken orally, weight gain has been reported by a single patient in a clinical trial (111773).

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General ...Orally, Lacticaseibacillus casei is generally well tolerated.
Most Common Adverse Effects:
Orally: Mild gastrointestinal adverse effects.
Serious Adverse Effects (Rare):
Orally: There is concern that lactobacilli may cause infections in some people.

Gastrointestinal ...Orally, taking Lacticaseibacillus casei in combination with other probiotics may cause gastrointestinal side effects including abdominal pain (90291); however, these events are uncommon.

Immunologic ...Since Lacticaseibacillus casei preparations contain live and active microorganisms, there is some concern that they might cause pathogenic infection in some patients. Some lactobacilli species have been isolated in some cases of bacteremia, sepsis, splenic abscess, endocarditis, aortic dissection, necrotizing fasciitis, pancreatic necrosis, and meningoencephalitis. Most of these cases are thought to be due to the translocation of bacteria from other locations in the body in which they occur naturally, such as the oral cavity and gastrointestinal tract. The majority of cases are not related to the use of probiotic supplements and most are not associated with the use of L. casei (107543,112516). There is at least one case of L. casei bacteremia and endocarditis thought to be related with L. casei intake in a 71-year-old immunocompromised female (112520).
There are two cases of L. casei infection in a prosthetic joint (90282,112514). In one case, the 95-year-old female with a history of hypertension, diabetes, and heart disease was known to consume yogurt containing L. casei. However, it was not confirmed that the infection was related to the consumption of this product. Spread from the gastrointestinal tract or vaginal flora could not be ruled out (90282). In the case of an 80-year-old male, the cause was unknown as there was no probiotic supplementation and no underlying medical condition or infectious portal of entry (112514).
A specific probiotic preparation (NBL probiotic ATP, Nobel) containing L. casei, Lacticaseibacillus rhamnosus, Lactiplantibacillus plantarum, Bifidobacterium animalis subsp. lactis, fructo-oligosaccharides, galacto-oligosaccharides, colostrum, and lactoferrin was found to be a significant risk factor for vancomycin-resistant Enterococcus colonization in premature infants. Although there was no direct link to determine causation, it was hypothesized that the probiotic mixture helped to mediate the acquisition and transfer of antibiotic resistance genes (96890).

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General ...Orally, Lacticaseibacillus paracasei is generally well tolerated.
Most Common Adverse Effects:
Orally: Mild gastrointestinal adverse effects.
Serious Adverse Effects (Rare):
Orally: There is concern that Lacticaseibacillus paracasei may cause infections in some people.

Dermatologic ...Orally, in one clinical trial, a combination of Lacticaseibacillus paracasei subsp. paracasei F19, Lactobacillus acidophilus La-5, and Bifidobacterium animalis subsp. lactis BB-12 was associated with two cases of rash, one with itching. However, it is not clear if these adverse effects were due to L. paracasei, other ingredients, the combination, or if the events were idiosyncratic (90236).
Topically, a lotion containing the cell free supernatant of L. paracasei was rarely associated with erythema, itching, and scaling (111945).

Gastrointestinal ...Orally, taking Lacticaseibacillus paracasei alone or in combination with other probiotics may cause gastrointestinal side effects including dyspepsia (105133), flatulence (107497), nausea (111952), and bloating (107497,111952); however, these events are uncommon.
There are at least five case reports of acute cholecystitis for which a lactobacilli was thought to be the primary pathogen. In a 66-year-old female, vancomycin-resistant L. paracasei was the primary pathogen resulting in peritonitis secondary to a cholecystitis-induced gallbladder perforation. Although the patient reportedly ate 96-128 oz of yogurt each day, this yogurt was not believed to be associated with the cholecystitis (103443).

Immunologic ...Since Lacticaseibacillus paracasei preparations contain live and active microorganisms, there is some concern that they might cause pathogenic infection in some patients. Lactobacilli species, including L. paracasei, have been isolated in some cases of bacteremia, sepsis, splenic abscess, endocarditis, necrotizing fasciitis, pancreatic necrosis, meningoencephalitis, and prosthetic joint infections. Most cases of L. paracasei infection are thought to be due to the translocation of bacteria from other locations in the body in which it occurs naturally, such as the oral cavity and gastrointestinal tract (107543,111942,111944,111946,90282). However, there are case reports of L. paracasei infections thought to be at least partially related to dietary or supplemental intake (90254,107546,95393). In a 77-year-old male who consumed yogurt containing L. paracasei daily, L. paracasei bacteremia with endocarditis was thought to be related to bacterial translocation from the colon following a colonoscopy (90254). In a 78-year-old male, L. paracasei bacteremia and endocarditis was thought to be related to daily use of probiotics; however, the specific species included in the product were not mentioned. Also, the patient was diagnosed with an aortic valve stenosis and had undergone dental treatment approximately 6 months previously, possibly increasing the risk for development of bacteremia (95393). In an immunocompetent 45-year-old male with no history of heart disease, consumption of yogurt containing L. paracasei for about 2.5 years was thought to be associated with the development of endocarditis (107546).

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General ...Orally, Lacticaseibacillus rhamnosus is generally well tolerated.
Most Common Adverse Effects:
Orally: Mild gastrointestinal adverse effects.
Serious Adverse Effects (Rare):
Orally: There is concern that L. rhamnosus may cause infections in some people.

Gastrointestinal ...Orally, taking Lacticaseibacillus rhamnosus alone or in combination with other probiotics may cause gastrointestinal side effects including diarrhea (90235); however, these events are uncommon. In one small clinical study in infants with suspected cow's milk allergy who were receiving extensively hydrolyzed whey formula, diarrhea occurred in 5 of 13 infants receiving non-viable, heat-killed L. rhamnosus, compared with 0 of 14 infants receiving live L. rhamnosus and 0 of 8 infants receiving placebo (107528).
A 31-year-old male developed severe L. rhamnosus GG stomatitis and oral ulcers while undergoing induction chemotherapy for acute myeloid leukemia. The strain in the ulcers was determined to be the same strain that had been consumed in dairy products (112506).

Immunologic ...Since Lacticaseibacillus rhamnosus preparations contain live and active microorganisms, there is some concern that they might cause pathological infection in some patients. Some lactobacilli species have been isolated in some cases of bacteremia, sepsis, splenic abscess, endocarditis, necrotizing fasciitis, pancreatic necrosis, and meningoencephalitis. Most of these cases are thought to be due to the translocation of bacteria from other locations in the body in which they occur naturally, such as the oral cavity and gastrointestinal system, in ill and/or immunocompromised patients, or in patients otherwise at risk of infection. However, there are also rare case reports of pathological infections possibly to intake of L. rhamnosus products in these populations (4380,4390,4391,4398,8561,13008,13070,90298,103444,105138)(105139,105141,107543,111613,112499,112505,112509,112536).
Case reports exist of bacteremia or sepsis associated with L. rhamnosus use in infants and children. In infants, some cases have occurred following the use of L. rhamnosus for the treatment or prevention of diarrhea. These cases include a severely ill 6-week-old infant given L. rhamnosus GG (Culturelle) for antibiotic-associated diarrhea (13008), a 6-day old with intrauterine growth restriction given L. rhamnosus GG to prevent antibiotic-associated diarrhea (112509), a 3-month-old infant given L. rhamnosus GG for the prevention of antibiotic-associated diarrhea, and a 18-day-old preterm, very-low-birthweight infant given L. rhamnosus GG for the prevention of necrotizing enterocolitis (111613). In other cases, infants with short bowel syndrome have developed bacteremia (13008,112536). One case report involved an 11-month-old infant receiving L. rhamnosus for 5 weeks through a gastrostomy tube for rotaviral diarrhea (13070). Lactobacillus sepsis has also occurred in a 6-year-old child with cerebral palsy following use of L. rhamnosus GG (Culturelle) for intermittent diarrhea (13008). A 17-year-old male with ulcerative colitis developed bacteremia following once daily use of L. rhamnosus GG 1 billion colony-forming units (CFUs) (Culturelle, ConAgra Foods) (90298).
There are also cases of L. rhamnosus bacteremia or sepsis in adults. Fatal L. rhamnosus septicemia has been reported in an immunocompromised patient consuming yogurt and taking prolonged courses of multiple broad spectrum antibiotics (8561). A 50-year-old male developed L. rhamnosus endocarditis following daily use of a probiotic product providing at least 5 billion CFUs of L. rhamnosus. Although the patient was considered healthy, the role of a previous diagnosis of an unspecified heart murmur or an untreated deep gingival cut 3 months prior to endocarditis diagnosis may have increased the risk of infection (105139). A 56-year-old immunocompetent female developed L. rhamnosus GG bacteremia. She was hospitalized with an indwelling catheter following a motor vehicle accident and had been given this strain following the onset of diarrhea via a nasogastric tube as per hospital protocol (112499). There is also a case of L. rhamnosus sepsis in a male in his late 60s with a bioprosthetic aortic valve. He was taking L. rhamnosus for ulcerative colitis and developed sepsis along with aortic valve endocarditis and septic emboli to the brain (112505).
A specific probiotic preparation (NBL probiotic ATP, Nobel) containing L. rhamnosus, Lacticaseibacillus casei, Lactiplantibacillus plantarum, Bifidobacterium animalis subsp. lactis, fructo-oligosaccharides, galacto-oligosaccharides, colostrum, and lactoferrin was found to be a significant risk factor for vancomycin-resistant Enterococcus colonization in premature infants. Although there was no direct link to determine causation, it was hypothesized that the probiotic mixture helped to mediate the acquisition and transfer of antibiotic resistance genes (96890).

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General ...Orally, Ligilactobacillus salivarius seems to be well tolerated.
Serious Adverse Effects (Rare):
Orally: There is concern that Ligilactobacillus salivarius may cause infections in some people.

Immunologic ...Since Ligilactobacillus salivarius preparations contain live and active microorganisms, there is some concern that they might cause pathogenic infection in some patients. Some lactobacilli species have been isolated in cases of bacteremia, sepsis, splenic abscess, endocarditis, necrotizing fasciitis, pancreatic necrosis, and meningoencephalitis. These cases are thought to be due to the translocation of bacteria from other locations in the body in which they occur naturally, such as the oral cavity, or the gastrointestinal or urogenital tract, and not to dietary or supplemental intake (107543,110917,110918,110920,110921). There are such examples of L. salivarius infection (112546,112552). In one case, a male developed an intrabdominal abscess following gastric bypass surgery (112552). In another, a 56-year-old male with diabetes and a previous gastrectomy developed bacteremia and empyema with respiratory failure (112546).

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