--- topic: "Lactobacillus Reuteri" title: "Gut Health, Immunity, and the Gut-Brain Axis" order: 1 description: "What clinical trials show for the probiotic Lactobacillus reuteri: shorter childhood diarrhea, a modest boost to H. pylori treatment, mixed results for infant colic, and early animal work on oxytocin" question: "Does Lactobacillus reuteri help diarrhea, infant colic and Helicobacter pylori?" answer: "Lactobacillus reuteri DSM 17938 probably shortens children's diarrhea by about a day and modestly improves Helicobacter pylori treatment success." actions: - "Choose the DSM 17938 strain used in most human trials, at 100 million to 1 billion CFU a day." - "If taking antibiotics, wait 2–3 hours before the probiotic and continue it for 1–2 weeks after the course ends." - "For colic in breastfed infants, the trial gave 100 million CFU (5 drops) daily for 21 days [3]." cautions: - "It was tested as an add-on to standard treatment for diarrhea and Helicobacter pylori, not a replacement [2][4]." - "Oxytocin and testosterone effects come from rodent studies; no human trial has shown them [7][8]." - "Gum-health trials reduced harmful bacteria but not gum bleeding or plaque at 8 weeks [6]." confidence: 4 confidenceNote: "Meta-analyses of 12 diarrhea RCTs and 8 H. pylori RCTs (1,087 patients) agree; colic rests on one 50-infant trial, and oxytocin findings are rodent-only." evidenceSummary: rctCount: 4 observationalCount: 0 metaAnalysisCount: 3 totalParticipants: "1,100+" replicated: true newestStudyYear: 2024 references: - id: "1" pmid: "29725324" title: "Role of Lactobacillus reuteri in Human Health and Diseases" authors: "Mu Q, Tavella VJ, Luo XM" year: 2018 journal: "Frontiers in Microbiology" - id: "2" pmid: "26991503" title: "Systematic review with meta-analysis: Lactobacillus reuteri DSM 17938 for diarrhoeal diseases in children" authors: "Urbańska M, Gieruszczak-Białek D, Szajewska H" year: 2016 journal: "Alimentary Pharmacology & Therapeutics" - id: "3" pmid: "20713478" title: "Lactobacillus reuteri DSM 17938 in infantile colic: a randomized, double-blind, placebo-controlled trial" authors: "Savino F, Cordisco L, Tarasco V, Palumeri E, Calabrese R, Oggero R, Roos S, Matteuzzi D" year: 2010 journal: "Pediatrics" - id: "4" pmid: "38846173" title: "Lactobacillus reuteri compared with placebo as an adjuvant in Helicobacter pylori eradication therapy: a meta-analysis of randomized controlled trials" authors: "Li M, Wang X, Dong X, Teng G, Dai Y, Wang W" year: 2024 journal: "Therapeutic Advances in Gastroenterology" - id: "5" pmid: "24381643" title: "Lactobacillus reuteri in management of Helicobacter pylori infection in dyspeptic patients: a double-blind placebo-controlled randomized clinical trial" authors: "Emara MH, Mohamed SY, Abdel-Aziz HR" year: 2014 journal: "Therapeutic Advances in Gastroenterology" - id: "6" pmid: "22694350" title: "Probiotic effects of orally administered Lactobacillus reuteri-containing tablets on the subgingival and salivary microbiota in patients with gingivitis: a randomized clinical trial" authors: "Iniesta M, Herrera D, Montero E, Zurbriggen M, Matos AR, Marín MJ, Sánchez-Beltrán MC, Llama-Palacio A, Sanz M" year: 2012 journal: "Journal of Clinical Periodontology" - id: "7" pmid: "27793228" title: "Microbes and Oxytocin: Benefits for Host Physiology and Behavior" authors: "Erdman SE, Poutahidis T" year: 2016 journal: "International Review of Neurobiology" - id: "8" pmid: "24392159" title: "Probiotic microbes sustain youthful serum testosterone levels and testicular size in aging mice" authors: "Poutahidis T, Springer A, Levkovich T, Qi P, Varian BJ, Lakritz JR, Ibrahim YM, Chatzigiagkos A, Alm EJ, Erdman SE" year: 2014 journal: "PLOS ONE" - id: "9" pmid: "29279326" title: "Lactobacillus reuteri to Treat Infant Colic: A Meta-analysis" authors: "Sung V, D'Amico F, Cabana MD, Chau K, Koren G, Savino F, Szajewska H, Deshpande G, Dupont C, Indrio F, Mentula S, Partty A, Tancredi D" year: 2018 journal: "Pediatrics" - id: "10" pmid: "24690625" title: "Treating infant colic with the probiotic Lactobacillus reuteri: double blind, placebo controlled randomised trial" authors: "Sung V, Hiscock H, Tang ML, Mensah FK, Nation ML, Satzke C, Heine RG, Stock A, Barr RG, Wake M" year: 2014 journal: "BMJ" --- Lactobacillus reuteri (now formally reclassified as Limosilactobacillus reuteri) is one of the best-studied probiotic bacteria in humans. Unlike many gut bacteria, it colonizes multiple body sites — the intestinal tract, urinary tract, skin, and breast milk [1]. Its abundance in humans has fallen over recent decades, a trend that parallels the rise in inflammatory diseases (a correlation, not proof of cause) [1]. Clinical trials have tested it for childhood diarrhea (where it shortened illness in treatment trials), H. pylori eradication (a modest boost to standard therapy), gum health (fewer periodontal pathogens, without a measurable clinical effect), and infant colic (where the trials disagree). Early work on the gut-brain axis suggests it may raise oxytocin, but that comes mainly from animal studies [7]. ## A Human-Adapted Bacterium L. reuteri is what researchers call a "human-adapted" commensal — a bacterium that lives on and in people at multiple body sites. It produces antimicrobial molecules such as organic acids, ethanol, and reuterin (3-hydroxypropionaldehyde), which help it inhibit the colonization of pathogenic microbes [1]. How much L. reuteri people carry varies from person to person, and the decline in its abundance in humans over past decades correlates with the rise in inflammatory diseases over the same period. That correlation has motivated research, but it does not show that the loss causes disease [1]. ## Two Strains, Two Roles Most of the human clinical research focuses on two strains: **DSM 17938** — the strain used in most gastrointestinal trials in children, including the diarrhea and infant colic trials described below [2][3][9][10]. **ATCC 6475** — studied mainly in animal work on oxytocin signaling and testosterone [7][8]. Human data on these effects are limited. ## Gut Health: Diarrhea and Infant Colic A 2016 systematic review of eight randomized trials (1,229 children) of L. reuteri DSM 17938 in diarrhoeal diseases found that, in three treatment trials (256 children), L. reuteri shortened the illness by about 25 hours on average (mean difference −24.8 hours, 95% CI −38.8 to −10.8) and raised the cure rate on days 1 and 2. The reviewers urged caution because the trials differed and the confidence intervals were wide. In preventive trials in hospitalised children, it did not significantly reduce hospital-acquired or rotavirus diarrhea [2]. For infantile colic — a condition in which otherwise healthy babies cry for hours a day — the trials disagree. - A double-blind trial in 50 exclusively breastfed colicky infants found that those given 10⁸ CFU a day of L. reuteri DSM 17938 had a median of 35 minutes of crying a day by day 21, compared with 90 minutes in the placebo group [3]. - A 2018 meta-analysis of four double-blind trials (345 infants) found that the probiotic group cried or fussed about 25 minutes a day less at day 21 and was almost twice as likely to reach treatment success; the effect was clear in breastfed infants and not significant in formula-fed infants, for whom there were too few data for conclusions [9]. - A larger community-based trial in 167 breastfed and formula-fed infants found no benefit: after one month the probiotic group cried or fussed 49 minutes a day *more* than the placebo group, mainly because of more fussing in formula-fed infants. Its authors concluded the findings do not support a general recommendation to use probiotics for colic [10]. The evidence therefore points to a possible benefit for some breastfed infants and no clear benefit more broadly. ## Helicobacter Pylori: A Modest Boost to Standard Therapy H. pylori is a stomach bacterium that causes peptic ulcers and is a risk factor for gastric cancer. Eradication rates with standard triple therapy (two antibiotics plus a proton pump inhibitor) are declining, and antibiotic resistance is a growing problem [4][5]. A 2024 meta-analysis of eight randomized trials (1,087 patients) found that adding L. reuteri to eradication therapy was followed by higher eradication rates in intention-to-treat analysis (80.0% vs. 72.6%, relative risk 1.10, 95% CI 1.03–1.17; about 14 patients treated for each extra eradication) and in per-protocol analysis (81.8% vs. 75.0%). Patients given L. reuteri also had greater improvement in gastrointestinal symptoms and fewer adverse events overall [4]. An individual trial in 70 treatment-naive patients with dyspepsia reached the same direction: standard triple therapy plus L. reuteri gave an eradication rate of 74.3% versus 65.7% with placebo, with less diarrhea and taste disturbance [5]. ## Oral Health: Targeting Periodontal Pathogens L. reuteri produces reuterin, which has antimicrobial activity [1]. In a randomized, placebo-controlled trial in 40 people with gingivitis, a daily L. reuteri tablet for 8 weeks lowered counts of selected periodontal pathogens, including *Porphyromonas gingivalis* in subgingival plaque (from baseline to 4 weeks), but it did not change the clinical signs of gingivitis during the trial [6]. Whether longer use or a different study design would show a clinical benefit is unknown. ## Oxytocin and the Gut-Brain Axis One of the more striking findings in L. reuteri research is its apparent ability to raise oxytocin. Oxytocin is known as a bonding hormone, but it has broad roles throughout the body, including wound healing and metabolism. In animal studies, L. reuteri has been found to up-regulate oxytocin and systemic immune responses, with reported effects on wound healing, mental health, metabolism, and bone maintenance [7]. These results suggest the gut microbiome interacts with the host through immune, endocrine, and brain signaling networks [7]. Controlled trials in people that measure oxytocin after L. reuteri supplementation are lacking, so this remains an area of research rather than an established clinical benefit. ## Immune Modulation Some L. reuteri strains can reduce the production of pro-inflammatory cytokines while promoting the development and function of regulatory T cells, and L. reuteri can strengthen the intestinal barrier, which may reduce the translocation of microbes from the gut into the tissues [1]. These effects, seen mainly in laboratory and animal studies, may underlie its effects in the conditions above, but that is a hypothesis. ## How to Supplement L. reuteri DSM 17938 is the strain with the broadest human trial base. The infant colic trials used 10⁸ CFU a day [3][10]. In the H. pylori trials, L. reuteri was given alongside standard antibiotic therapy [4][5]. See our [probiotics page](/probiotics/gut-microbiome) for broader context on cultivating a healthy microbiome, and our [gut-brain axis page](/gut-brain-axis) for more on microbial effects on mood and behavior. ## Evidence Review ### Systematic Review: Diarrhea in Children — Urbańska, Gieruszczak-Białek & Szajewska (2016) Urbańska and colleagues searched Medline, Embase, the Cochrane Library, and trial registries in January 2016 for randomized trials of L. reuteri DSM 17938 in the management of various types of diarrhoeal disease in children and included eight (n = 1,229) [2]. In treatment trials (three RCTs, n = 256), L. reuteri reduced the duration of diarrhea (mean difference −24.82 hours, 95% CI −38.8 to −10.8) and increased the cure rate on days 1 and 2; heterogeneity and wide confidence intervals call for caution. In preventive trials in hospitalised children (two RCTs, n = 290), L. reuteri did not significantly reduce the risk of hospital-acquired diarrhea, rotavirus diarrhea, or diarrhea of any origin. In one RCT (n = 97) it had no effect on the risk of antibiotic-associated diarrhea, although the overall frequency of diarrhea was surprisingly low. In preventive studies in apparently healthy children, L. reuteri reduced diarrhoeal outcomes in one RCT and the evidence from another was less convincing. The authors concluded that in therapeutic settings L. reuteri reduces the duration of diarrhea and increases the chance of cure, and that in preventive settings it has the potential to reduce the risk of community-acquired diarrhea in otherwise healthy children. ### Infantile Colic: Three Studies, Mixed Conclusions Savino et al. (2010) published a double-blind, placebo-controlled trial in *Pediatrics* testing L. reuteri DSM 17938 in 50 exclusively breastfed infants with colic, diagnosed by modified Wessel's criteria [3]. The infants received 10⁸ CFU a day or placebo for 21 days, and parents recorded daily crying time. Forty-six infants completed the trial (25 in the L. reuteri group, 21 in the placebo group). Median daily crying time was 370 versus 300 minutes at baseline (P = 0.127) and 35 versus 90 minutes at day 21 (P = 0.022). Responders (at least a 50% reduction in crying time) were significantly more frequent with L. reuteri on days 7 (20 vs 8), 14 (24 vs 13), and 21 (24 vs 15). Fecal lactobacilli rose and fecal *Escherichia coli* and ammonia fell in the L. reuteri group only. No adverse events related to the supplement were seen. The authors concluded that L. reuteri improved colic symptoms in early breastfed infants and suggested that gut microbiota changes could be involved. It was a small trial, restricted to exclusively breastfed infants. Sung et al. (2018) pooled individual participant data from four double-blind trials of L. reuteri DSM 17938 versus placebo involving 345 infants with colic (174 probiotic, 171 placebo) [9]. At day 21 the probiotic group averaged less crying or fussing time (adjusted mean difference in change from baseline −25.4 minutes, 95% CI −47.3 to −3.5) and was almost twice as likely to have treatment success (adjusted incidence ratio 1.7, 95% CI 1.4 to 2.2). The intervention effect was large in breastfed infants (number needed to treat for day-21 success 2.6, 95% CI 2.0 to 3.6) but insignificant in formula-fed infants, with too few data to draw conclusions for them. The authors concluded that L. reuteri DSM 17938 is effective and can be recommended for breastfed infants with colic. Sung et al. (2014) tested the same strain in a broader group [10]. In a double-blind, placebo-controlled trial in Melbourne, 167 breastfed or formula-fed infants under 3 months who met criteria for excessive crying or fussing were randomized to L. reuteri DSM 17938 (10⁸ CFU a day; 85 infants) or placebo (82 infants) for one month. Of the 167, 127 (76%) were retained to the primary outcome, which was the daily duration of crying or fussing at one month. Cry or fuss time fell steadily in both groups. At one month the probiotic group cried or fussed 49 minutes a day more than the placebo group (95% CI 8 to 90 minutes, P = 0.02), mainly because of more fussing, especially in formula-fed infants. The groups were similar on all secondary outcomes, and no study-related adverse events occurred. The authors concluded that L. reuteri DSM 17938 did not benefit a community sample of breastfed and formula-fed infants with colic, that the findings differ from previous smaller trials of selected populations, and that they do not support a general recommendation for probiotics to treat colic. Together these studies show a possible benefit in some breastfed infants, concentrated in small trials of selected populations and in a pooled analysis, and no benefit in a larger community trial that also included formula-fed infants. ### H. Pylori Meta-Analysis: Li et al. (2024) Li et al. performed a meta-analysis of eight randomized controlled trials with 1,087 patients comparing L. reuteri supplementation with placebo alongside H. pylori eradication therapy [4]. The primary outcome was the H. pylori eradication rate; the Gastrointestinal Symptom Rating Scale and adverse events were secondary outcomes. In the pooled analysis: - Intention-to-treat eradication rate: 80.0% (L. reuteri) vs. 72.6% (placebo); p = 0.005, relative risk 1.10 (95% CI 1.03–1.17), number needed to treat 14 - Per-protocol eradication rate: 81.8% vs. 75.0%; p = 0.006, relative risk 1.09 (95% CI 1.03–1.16), number needed to treat 15 - Gastrointestinal symptoms: greater improvement with L. reuteri (pooled mean difference −2.43, 95% CI −4.56 to −0.29, p = 0.03) - Adverse events: significantly fewer with L. reuteri (relative risk 0.72, 95% CI 0.67–0.78 in the intention-to-treat analysis) The benefit is modest — roughly 7 percentage points of eradication — but consistent in direction across the pooled trials. The authors concluded that L. reuteri supplementation improved the eradication rate, reduced side effects, and relieved gastrointestinal symptoms during treatment. ### H. Pylori RCT: Emara et al. (2014) Emara and colleagues conducted a double-blind placebo-controlled trial in 70 treatment-naive H. pylori-positive patients with dyspepsia [5]. Patients received standard triple therapy for 2 weeks plus either L. reuteri or placebo for 4 weeks and were re-examined 4 weeks after treatment. Eradication rates were 74.3% with L. reuteri and 65.7% with placebo, a difference of 8.6 percentage points. Patients given L. reuteri reported less diarrhea and fewer taste disorders, improved more on the Gastrointestinal Symptom Rating Scale, and had a greater improvement in the histological severity and activity of H. pylori gastritis than the placebo group. The abstract does not state whether the difference in eradication rate was statistically significant. ### Oral Health: Iniesta et al. (2012) Iniesta and colleagues conducted an 8-week, placebo-controlled, parallel-group trial in 40 people with gingivitis [6]. Participants took a daily tablet containing L. reuteri or placebo. Saliva and subgingival plaque samples were analyzed by culture and PCR. There were no significant changes in the clinical variables between or within groups. In saliva, total anaerobic counts at 4 weeks (p = 0.021) and *Prevotella intermedia* counts at 8 weeks (p = 0.030) fell in the test group. In subgingival samples, the changes from baseline to 4 weeks in *P. gingivalis* counts were significantly reduced (p = 0.008). With PCR, strain ATCC PTA 5289 was detected more often than DSM 17938. The authors concluded that L. reuteri tablets reduced selected periodontal pathogens in the subgingival microbiota, without an associated clinical impact. ### Oxytocin: Erdman & Poutahidis (2016) Erdman and Poutahidis reviewed the evidence linking L. reuteri to oxytocin [7]. They describe L. reuteri as a prototype probiotic bacterium that has been found to upregulate oxytocin and systemic immune responses, with benefits reported for wound healing, mental health, metabolism, and musculoskeletal maintenance, and they argue that the gut microbiome and the host interact through immune-endocrine-brain signaling networks. The work discussed is largely preclinical, and the review is a summary rather than a clinical trial. The references in this article include no controlled human trial that measures oxytocin in response to L. reuteri supplementation. ### Testosterone: Poutahidis et al. (2014) Poutahidis et al. reported that male mice drinking *L. reuteri* in their water had larger testicles, increased spermatogenesis, and more Leydig cells (the testosterone-producing cells) per testis than matched controls, together with higher serum testosterone [8]. Blocking the pro-inflammatory cytokine interleukin-17A with antibodies restored testicular mass and other indicators of old age to youthful levels, which indicated that uncontrolled host inflammatory responses contributed to testicular atrophy in aged mice. This is mouse data. A 2024 human trial of the same strain in healthy men aged 55–65 found no effect on testosterone; see our [L. reuteri overview](/probiotics/lactobacillus-reuteri). ### Strength of Evidence The clinical evidence for L. reuteri is strongest for the conditions with several trials and a pooled analysis: shortening of childhood diarrhea in treatment settings, and a modest improvement in H. pylori eradication with fewer side effects. Infant colic is the clearest example of mixed evidence: small trials and a pooled analysis suggest a benefit in some breastfed infants, while a larger community trial found none. Oral health evidence shows changes in bacterial counts but not in clinical signs of gum disease. The oxytocin and testosterone findings are intriguing signals from animal work that have not been validated in human trials.