Lactobacillus Reuteri
How this ancient human-compatible probiotic strain supports bone density, hormonal balance, gut health, and the gut-brain connection
Lactobacillus reuteri (now formally called Limosilactobacillus reuteri) is one of the few probiotic species that colonized human guts long before modern diets displaced it. Research over the past two decades has uncovered an unusually wide range of documented effects — from reducing infant colic [4] to slowing bone loss in older women [2] to upregulating the social bonding hormone oxytocin [3]. Unlike many probiotic strains studied only in the lab, L. reuteri has multiple randomized controlled trials in humans, making it one of the best-evidenced specific probiotic strains available.
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 best-studied strain for digestive health. It has the most evidence for reducing infant colic, easing acute diarrhea, and supporting gut motility. Most pediatric L. reuteri studies use this strain.
ATCC PTA 6475 is the strain featured in the bone density and testosterone research. It produces higher amounts of certain bioactive compounds and has been used in studies examining hormonal and musculoskeletal health. Many of the 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 stimulate the release of oxytocin — the hormone associated with social bonding, trust, and wound healing [3]. In animal studies, mice fed L. reuteri showed faster wound healing, improved social behavior, and thicker, more lustrous fur. When researchers blocked oxytocin signaling in the brain, the wound healing effect disappeared, confirming oxytocin as the mechanism. The bacteria appear to act through the vagus nerve to signal the hypothalamus to produce more oxytocin.
Whether this translates fully to humans is still being studied, but the gut-to-brain signaling pathway is real and measurable.
Bone Density in Older Women
The ELBOW (Effects of Lactobacillus reuteri on Bone in Older Women) trial is one of the most compelling human studies. Ninety women aged 75–80 with low bone mineral density were randomized to receive L. reuteri ATCC PTA 6475 (10 billion CFU daily) or placebo for 12 months. Those taking the probiotic lost significantly less bone mass than the placebo group — about half the bone loss [2]. The proposed mechanism involves gut bacteria modulating immune-mediated osteoclast activity, the cell type responsible for breaking down bone tissue.
This effect fits a broader picture: gut dysbiosis is linked to increased inflammatory signaling that accelerates bone resorption. Restoring a healthy microbiome may dampen this inflammatory cascade.
Testosterone and Hormonal Health
Animal data from MIT showed that aging male mice consuming L. reuteri had larger testes, higher testosterone levels, and increased Leydig cell numbers compared to controls [1]. The effect was dramatic enough to reverse the testicular atrophy that normally accompanies aging in these animals. The mechanism involves reduced systemic inflammation lowering the inhibitory signals that suppress gonadal testosterone production.
Human clinical trials have been more modest. A 2024 double-blind randomized trial with 12 weeks of L. reuteri supplementation in men aged 55–65 found no significant change in serum testosterone [5]. However, the pilot data from Japanese research did show reductions in body fat percentage and inflammatory markers. The honest summary: the testosterone effects in aging humans remain unproven, though the mechanistic pathway is biologically plausible and the animal evidence is robust.
Infant Colic and Digestive Health
L. reuteri DSM 17938 is the most evidence-backed intervention for breastfed infant colic. Multiple randomized trials and a 2018 meta-analysis of over 500 infants found that daily supplementation (100 million CFU) reduced crying time by roughly 25 minutes per day at three weeks, with the probiotic group almost twice as likely to experience treatment success [4][6]. The effect is strongest in breastfed infants; results in formula-fed infants have been inconsistent across studies.
Using L. Reuteri
Standard commercial doses range from 100 million to 10 billion CFU depending on the strain and health goal. For the bone density research protocol, ATCC PTA 6475 at 10 billion CFU daily was used. For infant colic, DSM 17938 at 100 million CFU is the studied dose.
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.
L. reuteri is well-tolerated in trials with no significant adverse effects. It is one of the most ancient human gut symbionts identified, present in traditional populations' microbiomes but largely absent from people eating industrialized diets.
See the Probiotics overview and specific strains guide for broader context on probiotic use.
Evidence Review
Testosterone: Animal vs. Human Evidence
Poutahidis et al. (2014, PLoS One, PMID 24392159) fed aging male mice L. reuteri ATCC PTA 6475 and compared them to age-matched controls eating a standard Western-style diet. The probiotic group showed significantly larger testes (by cross-sectional area), higher serum testosterone, increased spermatogenesis, and a greater number of Leydig cells per testis. The mechanism proposed was systemic reduction of pro-inflammatory IL-17 signaling, which normally suppresses Leydig cell activity as animals age. This was a well-controlled animal study, but it cannot be directly extrapolated to humans.
The human counterpart, Ljunggren et al. (2024, Contemporary Clinical Trials Communications, PMID 38770015), conducted a 12-week double-blind, placebo-controlled RCT in men aged 55–65, using both high- and low-dose L. reuteri ATCC PTA 6475. Neither dose produced a statistically significant change in serum testosterone compared to placebo. Secondary outcomes included modest improvements in metabolic markers in some participants. The study was relatively short and used a relatively healthy population, leaving open whether longer duration or different populations (with lower baseline testosterone) might show a different result. Current evidence does not support L. reuteri as a testosterone booster in healthy older men.
Bone Mineral Density: Strong Human RCT Evidence
Nilsson et al. (2018, Journal of Internal Medicine, PMID 29926979) — the ELBOW trial — remains the flagship human study for L. reuteri and bone health. Ninety postmenopausal women (75–80 years, low baseline BMD) received 10 billion CFU of L. reuteri ATCC PTA 6475 or placebo daily for 12 months. Seventy participants completed the study. The primary outcome, total volumetric bone mineral density (vBMD), decreased by 2.6% in the placebo group but only 0.83% in the probiotic group (p=0.046) — representing approximately a 68% reduction in bone loss rate. Secondary tibial cortical bone measures showed similar trends. No serious adverse events were reported. Limitations include the single-centre design and modest sample size; replication in larger multicenter trials would strengthen confidence.
The proposed mechanism involves the gut microbiome modulating RANKL/OPG signaling in intestinal immune cells. L. reuteri may reduce intestinal permeability and lower systemic LPS (lipopolysaccharide), which in turn decreases RANKL-driven osteoclastogenesis — the cellular process that breaks down bone.
Oxytocin Upregulation: Animal Evidence with Mechanistic Clarity
Varian et al. (2017, Brain, Behavior, and Immunity, PMID 27825953) demonstrated that dietary L. reuteri lysate — heat-killed bacteria, not live — was sufficient to increase oxytocin-positive cells in the paraventricular nucleus of the hypothalamus in mice and to accelerate wound healing. The effect was abolished by vagotomy (cutting the vagus nerve) and by oxytocin receptor blockade, confirming the gut-vagus-hypothalamus pathway. The study used ATCC PTA 6475. While this is animal research, it provides a mechanistic framework for the anti-inflammatory and social behavioral effects observed in probiotic-treated animals and connects to the broader field of psychobiotics.
Infant Colic: Multiple RCTs with Consistent Results in Breastfed Infants
Savino et al. (2010, Pediatrics, PMID 20713478) randomized 50 breastfed colicky infants to L. reuteri DSM 17938 (100 million CFU/day) or placebo simethicone. After 21 days, 95% of the probiotic group were treatment responders (defined as ≥50% reduction in crying time) compared to 7% in the simethicone group. Crying time fell from ~197 minutes/day to ~51 minutes/day in the probiotic group.
The 2018 meta-analysis by Sung et al. (Pediatrics, PMID 29279326) pooled 12 RCTs (n=561 infants) and found probiotic-treated infants cried an average of 25.4 fewer minutes per day at day 21 compared to controls (adjusted mean difference). The number needed to treat for response was approximately 2.6 in breastfed infants. Effect sizes in formula-fed infants were not statistically significant, suggesting a different etiology or microbiome context. The overall quality of evidence for breastfed infant colic is rated moderate to high.
Evidence Strength Summary
| Outcome | Population | Evidence Level | Verdict |
|---|---|---|---|
| Infant colic reduction | Breastfed infants | Multiple RCTs + meta-analysis | Strong for breastfed infants |
| Bone mineral density preservation | Postmenopausal women | Single RCT (n=90) | Promising, needs replication |
| Testosterone preservation | Aging men | 1 negative RCT, strong animal data | Unproven in humans |
| Oxytocin upregulation | Animal models | Multiple mechanistic studies | Plausible, not yet confirmed in humans |
References
- Probiotic microbes sustain youthful serum testosterone levels and testicular size in aging micePoutahidis T, Springer A, Bharwani A, Everard A, Tokita K, Kearney SM, Erdman SE. PLoS One, 2014. PubMed 24392159 →
- Lactobacillus reuteri reduces bone loss in older women with low bone mineral density: a randomized, placebo-controlled, double-blind, clinical trialNilsson AG, Sundh D, Bäckhed F, Lorentzon M. Journal of Internal Medicine, 2018. PubMed 29926979 →
- Microbial lysate upregulates host oxytocinVarian 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. Brain, Behavior, and Immunity, 2017. PubMed 27825953 →
- Lactobacillus reuteri DSM 17938 in infantile colic: a randomized, double-blind, placebo-controlled trialSavino F, Cordisco L, Tarasco V, Palumeri E, Calabrese R, Oggero R, Roos S, Matteuzzi D. Pediatrics, 2010. PubMed 20713478 →
- Effects of probiotic supplementation on testosterone levels in healthy ageing men: A 12-week double-blind, placebo-controlled randomized clinical trialLjunggren L, Butler E, Axelsson J, Åström M, Ohlsson L. Contemporary Clinical Trials Communications, 2024. PubMed 38770015 →
- Lactobacillus reuteri to treat infant colic: a meta-analysisSung V, D'Amico F, Cabana MD, Chau K, Koren G, Savino F, Szajewska H, Deshpande G, Dupont C, Indrio F, Mentula S, Partty A, Tanaka M. Pediatrics, 2018. PubMed 29279326 →
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