--- topic: "Probiotics" title: "Lactobacillus Reuteri" order: 4 description: "What trials show for this human-associated probiotic strain: bone density, hormones, gut health, and the mixed evidence on infant colic" question: "What is the probiotic Lactobacillus reuteri actually good for?" answer: "Lactobacillus reuteri likely eases colic in breastfed babies; the bone-loss benefit rests on one trial, and testosterone effects were not confirmed in men." actions: - "Match the strain to the goal: DSM 17938 was studied for infant colic, ATCC PTA 6475 for bone and hormone research [2][4]." - "Doses studied: 100 million CFU daily (DSM 17938) for colic [4], and 10 billion CFU daily (ATCC PTA 6475) for 12 months for bone loss [2]." cautions: - "Give to infants only after checking with a pediatrician; benefit was seen in breastfed babies and was inconsistent in formula-fed ones [6]." - "A 12-week trial in men aged 55–65 found no significant change in testosterone, so it is not a proven testosterone booster [5]." - "Home-fermented L. reuteri yogurt has not been formally evaluated in clinical trials." confidence: 3 confidenceNote: "Colic: a 12-trial meta-analysis (561 infants); bone: one 90-woman RCT; testosterone: one null human RCT; oxytocin: mouse studies only." evidenceSummary: rctCount: 3 observationalCount: 0 metaAnalysisCount: 1 totalParticipants: "650+" replicated: true newestStudyYear: 2024 references: - id: "1" 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: "2" pmid: "29926979" title: "Lactobacillus reuteri reduces bone loss in older women with low bone mineral density: a randomized, placebo-controlled, double-blind, clinical trial" authors: "Nilsson AG, Sundh D, Bäckhed F, Lorentzon M" year: 2018 journal: "Journal of Internal Medicine" - id: "3" pmid: "27825953" title: "Microbial lysate upregulates host oxytocin" authors: "Varian BJ, Poutahidis T, DiBenedictis BT, Levkovich T, Ibrahim Y, Didyk E, Shikhman L, Cheung HK, Hardas A, Ricciardi CE, Kolandaivelu K, Veenema AH, Alm EJ, Erdman SE" year: 2017 journal: "Brain, Behavior, and Immunity" - id: "4" 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: "5" pmid: "38770015" title: "Effects of probiotic supplementation on testosterone levels in healthy ageing men: A 12-week double-blind, placebo-controlled randomized clinical trial" authors: "Ljunggren L, Butler E, Axelsson J, Åström M, Ohlsson L" year: 2024 journal: "Contemporary Clinical Trials Communications" - id: "6" 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: "7" 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 called Limosilactobacillus reuteri) is a probiotic species that lives naturally in human guts and other body sites. Research over the past two decades has examined an unusually wide range of possible effects — from easing crying in some breastfed babies with colic [4][6] to slowing bone loss in older women [2] to raising the social bonding hormone oxytocin in mice [3]. L. reuteri has been tested in human randomized controlled trials for several of these uses, but the results are mixed: some trials found benefits, and others, including a large infant colic trial and a testosterone trial in men, found none [5][7]. ## Two Key Strains Not all L. reuteri supplements are the same. The strain number matters, because different strains have been studied for different outcomes: **DSM 17938** is the strain used in most pediatric and digestive trials, including the infant colic studies discussed below [4][6][7]. **ATCC PTA 6475** is the strain featured in the bone density and testosterone trials [2][5]. Some popular "super yogurt" fermentation protocols use this strain. ## The Oxytocin Connection One of the more striking discoveries from MIT researchers is that L. reuteri appears to raise levels of oxytocin — the hormone associated with social bonding, trust, and wound healing [3]. In mice, feeding L. reuteri raised oxytocin and speeded skin wound healing, and in the 2017 study even a sterile lysate of the bacteria (so, not live organisms) was enough to boost systemic oxytocin and improve wound repair. The same report states that the wound-repair benefit of oral L. reuteri extended to human subjects. The oxytocin findings are largely from animal experiments, though, and a human effect on oxytocin has not been established. ## Bone Density in Older Women In a randomized, double-blind, placebo-controlled trial, women aged 75–80 with low bone mineral density took L. reuteri ATCC PTA 6475 (10 billion CFU daily) or placebo for 12 months. Ninety women were enrolled and 70 completed the study. The probiotic group lost less bone density at the tibia than the placebo group — about 0.8% versus about 1.9% — although the effects on secondary bone measures were smaller and not statistically significant in the main analysis [2]. The trial was designed to test whether findings from mice carry over to people; how the probiotic might act on bone in humans is not known. ## Testosterone and Hormonal Health Animal data from MIT showed that aging male mice drinking L. reuteri had larger testes, higher testosterone levels, and more Leydig cells (the cells that make testosterone) than matched controls [1]. Blocking the inflammatory signal interleukin-17A restored testicular size in a similar way, which suggested that inflammation contributes to testicular shrinkage in aged mice. Human trial data are less encouraging. A 2024 double-blind randomized trial of 12 weeks of L. reuteri ATCC PTA 6475 in healthy men aged 55–65 found no effect on testosterone levels at either a high or low dose, although triglyceride levels fell significantly in the high-dose group [5]. The honest summary: the testosterone effects seen in mice have not been shown in men. ## Infant Colic and Digestive Health L. reuteri DSM 17938 is the most studied probiotic for infant colic, but the trials disagree. - **Small trials found benefits in breastfed babies.** In a trial of 50 exclusively breastfed colicky infants, 10⁸ CFU a day for 21 days was followed by median crying of 35 minutes a day, against 90 minutes with placebo [4]. - **A pooled analysis found a modest average benefit.** A 2018 meta-analysis of individual data from four double-blind trials (345 infants) found that the probiotic group cried or fussed about 25 minutes a day less than the placebo group at day 21 and was almost twice as likely to reach treatment success. The effect was clear in breastfed infants (about 3 babies treated for each extra success) and not significant in formula-fed infants, for whom the authors said there were too few data to draw conclusions [6]. - **A larger community trial found no benefit.** In a double-blind trial of 167 breastfed and formula-fed infants under 3 months in Melbourne, Australia, the group given 10⁸ CFU a day for a month cried or fussed 49 minutes a day *more* than the placebo group at one month (95% CI 8 to 90 minutes), mainly because of more fussing, especially in formula-fed babies. The authors concluded that the finding does not support a general recommendation to use probiotics for colic [7]. Taken together, the evidence suggests a possible benefit in some breastfed infants with colic in selected populations, and no clear benefit in a broader community sample or in formula-fed infants. ## Using L. Reuteri Doses in the trials above ranged from 100 million CFU (infant colic, DSM 17938) to 10 billion CFU a day (bone density, ATCC PTA 6475) [2][4][7]. Some people ferment L. reuteri into yogurt (using ATCC PTA 6475 or DSM 17938 tablets as starter) to achieve higher concentrations than supplements typically provide. This approach has become popular but lacks formal clinical evaluation at the fermented-food dose. No adverse events attributable to the probiotic were reported in the bone density and infant colic trials above, and adverse events did not differ from placebo in the bone trial [2][4][7]. See the [Probiotics overview](/probiotics/gut-microbiome) and [specific strains guide](/probiotics/strains-that-matter) for broader context on probiotic use. ## Evidence Review ### Testosterone: Animal vs. Human Evidence Poutahidis et al. (2014, PLoS One, PMID 24392159) found that male mice routinely drinking purified L. reuteri had larger testicles and higher serum testosterone than age-matched controls; microscopy showed significantly larger seminiferous tubule cross-sectional profiles and more spermatogenesis and Leydig cells per testis [1]. The authors then tested whether this reflected anti-inflammatory properties of L. reuteri and found that 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 the testicular atrophy of aged mice. This was a well-controlled animal study, but it cannot be extrapolated directly to humans. The human counterpart, Ljunggren et al. (2024, Contemporary Clinical Trials Communications, PMID 38770015), was a 12-week randomized, double-blind, placebo-controlled trial in healthy men aged 55–65, using a high dose, a low dose, or placebo of L. reuteri ATCC PTA 6475 [5]. Blood was sampled at baseline, 6 weeks, and 12 weeks. The supplement had no effect on testosterone at either dose. The only significant change in the other parameters measured was a decrease in triglyceride levels in the high-dose group. The authors concluded that the study does not support the hypothesis that a probiotic can raise testosterone in ageing men. It was a short study in healthy men, so it cannot say whether longer treatment or men with low testosterone would respond differently. ### Bone Mineral Density: A Single Human RCT Nilsson et al. (2018, Journal of Internal Medicine, PMID 29926979) is the only human trial of L. reuteri and bone in this review [2]. Women aged 75–80 with low bone mineral density were randomized to 10¹⁰ CFU of L. reuteri ATCC PTA 6475 daily or placebo. The predefined primary end point was the relative change after 12 months in total volumetric bone mineral density (vBMD) of the tibia. Ninety women were included and 70 completed the study. In the intention-to-treat analysis, vBMD changed by −0.83% (95% CI −1.47 to −0.19) with L. reuteri versus −1.85% (95% CI −2.64 to −1.07) with placebo, a mean difference of 1.02% (95% CI 0.02 to 2.03). The per-protocol analysis gave a similar result (−0.93% vs −1.86%; difference 0.93%, 95% CI 0.21 to 1.65). In general, similar but smaller effects were seen on the secondary bone variables, but these differences did not reach statistical significance in the intention-to-treat population. Adverse events did not differ between groups. The authors concluded that the approach should be explored further. The confidence interval for the main result is close to zero at its lower end, and replication in larger trials is needed. ### Oxytocin: Mostly Animal Evidence Varian et al. (2017, Brain, Behavior, and Immunity, PMID 27825953) reported that feeding L. reuteri raises endogenous oxytocin and improves skin wound healing in mice, and that this wound-repair benefit of oral L. reuteri extended to human subjects [3]. They also showed that dietary supplementation with a sterile lysate of the microbe was enough to raise systemic oxytocin levels and improve wound repair. In mice fed the lysate, oxytocin-producing cells increased in the caudal paraventricular nucleus of the hypothalamus, blood levels of the stress hormone corticosterone were lower, and the epidermis closed more rapidly. The authors concluded that microbe viability is not essential for regulating host oxytocin levels, and that a peptide or metabolite produced by the bacteria may modulate oxytocin secretion. The oxytocin results themselves come from mice. ### Infant Colic: Conflicting Trials Savino et al. (2010, Pediatrics, PMID 20713478) randomized 50 exclusively breastfed infants with colic to L. reuteri DSM 17938 (10⁸ CFU a day) or placebo for 21 days; 46 completed the trial (25 in the probiotic group, 21 in the placebo group) [4]. Median daily crying time was 370 versus 300 minutes at the start (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 increased and fecal *E. coli* and ammonia decreased in the L. reuteri group only. No adverse events related to the supplement were observed. This was a small trial, in exclusively breastfed infants, from one research group. The 2018 individual-participant-data meta-analysis by Sung et al. (Pediatrics, PMID 29279326) pooled four double-blind trials of L. reuteri DSM 17938 versus placebo involving 345 infants with colic (174 probiotic, 171 placebo) [6]. At day 21 the probiotic group averaged less crying or fussing than the placebo group (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 effect was large in breastfed infants (number needed to treat for day-21 success 2.6, 95% CI 2.0 to 3.6) and insignificant in formula-fed infants, and there were insufficient data to draw conclusions for formula-fed infants. The authors concluded that L. reuteri DSM 17938 is effective and can be recommended for breastfed infants with colic, and that its role in formula-fed infants needs further research. Sung et al. (2014, BMJ, PMID 24690625), the Baby Biotics trial, took a different approach: a community-based sample [7]. A total of 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 in primary and secondary care centers in Melbourne. The primary outcome was daily crying or fussing duration at one month, with 127 infants (76%) retained to that point. Mean daily 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 reflecting more fussing, especially in formula-fed infants. The groups were similar on all secondary outcomes (including sleep, maternal mental health, family functioning, fecal microbial diversity, *E. coli* colonization, and calprotectin), 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 earlier smaller trials in selected populations, and that they do not support a general recommendation to use probiotics to treat colic. Why the trials disagree is not settled. The earlier positive trials were smaller, the meta-analysis found the benefit concentrated in breastfed infants, and the null trial enrolled both breastfed and formula-fed infants from the community. Crying also fell steadily in the placebo groups (from a median of 300 to 90 minutes a day in the 2010 trial [4], and in both groups in the 2014 trial [7]), which is why placebo-controlled designs matter for a condition that tends to improve with time. ### Evidence Strength Summary | Outcome | Population | Evidence Level | Verdict | |---|---|---|---| | Infant colic | Breastfed infants | Small RCTs and an individual-data meta-analysis (positive) | Possible benefit; not consistent | | Infant colic | Breastfed and formula-fed community sample | One larger RCT (negative) | No benefit; probiotic group cried more | | Infant colic | Formula-fed infants | Insufficient data in the meta-analysis; worse crying in the community trial | Not supported | | Bone mineral density preservation | Older women with low bone density | Single RCT (n=90, 70 completed) | Promising, needs replication | | Testosterone preservation | Aging men | One negative RCT; positive mouse data | Not shown in humans | | Oxytocin upregulation | Mostly animal models | Mouse experiments; a reported human wound-repair effect | Plausible, not established for oxytocin in humans |