Lactobacillus reuteri

Lactobacillus reuteri (Limosilactobacillus reuteri)

1. Identity

Nomenclature and Taxonomy

Lactobacillus reuteri has undergone several taxonomic revisions. At the turn of the 20th century it was recorded in scientific classifications of lactic acid bacteria but was mistakenly grouped as a member of Lactobacillus fermentum. In the 1960s, German microbiologist Gerhard Reuter reclassified it as L. fermentum biotype II. Significant differences were eventually found between biotype II and other L. fermentum biotypes, and in 1980 it was formally recognised as a distinct species under the name Lactobacillus reuteri. In April 2020, the species was reassigned to the new genus Limosilactobacillus, making its current valid binomial Limosilactobacillus reuteri (Ligilactobacillus nomenclature, 2020). The older name Lactobacillus reuteri remains widely used in the scientific and clinical literature and is retained throughout this article for clarity.

The species was formally identified as distinct in 1980 by Kandler et al., who chose the species epithet reuteri in honour of its discoverer Gerhard Reuter.

Lactobacillus reuteri is a heterofermentative lactic acid bacterium that naturally inhabits the gut of humans and other animals. It is a Gram-positive bacterium whose principal natural habitat is the digestive tract of mammals and birds.

Natural Sources and Ecological Niches

L. reuteri is a heterofermentative lactic acid bacterium found in a variety of ecological niches, including food fermentations such as sourdough, meat, and dairy products, as well as the gastrointestinal and urogenital tracts of humans and other animals.

Lactobacillus reuteri is a natural resident of mammalian and avian gastrointestinal tracts as well as the human urogenital tract and breast milk. The animal GI tract appears to be the species' main habitat, and because L. reuteri was found to be the most predominant Lactobacillus in the intestine of a large number of animals and humans alike, it has been suggested to be the "universal enterolactobacillus."

L. reuteri is one of very few probiotic species whose natural habitat is the digestive tract, making it especially well adapted to thrive in that environment. It is among the first bacterial species to become naturally established in the normal microbiota of the newborn. Most other probiotic strains are only temporary or transient inhabitants of the gastrointestinal tract, derived from food intake.

In humans specifically, L. reuteri has been isolated from breast milk, the mouth, the stomach, the small intestine (duodenum and ileum), the colon, faeces, and the vagina.

L. reuteri is considered an autochthonous resident, meaning it is one of the few species naturally indigenous to the gastrointestinal tract of mammals, including humans. It is characterised as a heterofermentative bacterium, capable of producing multiple end products from carbohydrate fermentation, not just lactic acid.

Finding high concentrations of L. reuteri in standard commercial foods is difficult, setting it apart from many other probiotics. Although historically isolated from human breast milk, its presence in the modern Western diet is not widespread. It is not typically a dominant species in starter cultures used for mass-produced fermented products such as commercial yogurts, sauerkraut, or pickles.

Common Preparations and Commercial Forms

There are many different strains of L. reuteri. Each strain has a slightly different genetic makeup, meaning the effect of the probiotic can vary between strains. The most commonly studied strains for infantile colic and gastrointestinal health are DSM 17938 and ATCC 55730. For oral health, most studies have used strains DSM 17938 and ATCC PTA 5289. Other studied strains include ATCC PTA 6475, RC-14, NCIMB 30242, and DSM 17648.

In 2007, two plasmids carrying antibiotic resistance genes (tetracycline and lincomycin) were removed from the parent strain ATCC 55730 to enhance safety, and the resulting modified strain was deposited at the German Centre for the Conservation of Microbial Species (DSMZ) and designated L. reuteri DSM 17938. L. reuteri ATCC 55730 is no longer available commercially but is considered relatively equivalent to its daughter strain DSM 17938.

Commercial preparations are available as:

• Oral drops (liquid suspension in oil — predominantly used in infants)
• Chewable tablets and lozenges
• Capsules and hard-shell capsules
• Sachets (powder for reconstitution)
• Fermented food products and yogurts formulated with specific strains

Dosages of L. reuteri in studies have ranged from 1 × 10⁷ (ten million) to 1 × 10¹¹ (one hundred billion) colony-forming units (CFUs) per day, for durations of 5 days to 6 months. In children and infants, dosages have usually been limited to 1 × 10⁹ (one billion) CFUs daily.

2. Traditional and Historical Use

L. reuteri, as a formally isolated and characterised bacterial species, has no documented history of deliberate traditional use. Its formal discovery dates only to the 20th century, and its identity as a distinct species was not confirmed until 1980. However, its context within broader fermentation traditions is relevant.

While Lactobacillus reuteri was only formally identified in 1962 from the gut of a healthy human by Dr. Gerhard Reuter, the physiological benefits it provides have been indirectly harnessed for generations through fermented foods and breast milk.

Although it was not isolated until the 20th century, the types of benefits now associated with L. reuteri — gut comfort, immune defence, and microbial protection — were long observed in traditional practices involving fermented foods and maternal care.

Lactobacillus reuteri is a dominant member of the intestinal microbiota of vertebrates and also occurs in food fermentations. The stable presence of L. reuteri in sourdough provides the opportunity to study the adaptation of vertebrate symbionts to an extra-intestinal habitat.

Isolation from traditional fermented foods has been documented across multiple cultures. L. reuteri has been isolated from homemade highland barley wines produced on the Tibetan Plateau, where highland barley — the main grain crop — is made into a variety of conventional fermented foods. Homemade highland barley wine may spontaneously undergo a secondary malolactic fermentation step by lactic acid bacteria. Similarly, L. reuteri strains from sourdough fermentations have been maintained by continuous industrial propagation since at least the 1970s.

The use of L. reuteri as a deliberate probiotic supplement is a modern development, originating from research that began in the 1980s and expanding commercially from the 1990s onward, primarily through clinical work conducted in Sweden with strains later commercialised under the BioGaia brand.

3. Key Constituents and Active Compounds

Primary Antimicrobial Metabolites

Reuterin (3-Hydroxypropionaldehyde / 3-HPA)

The probiotic effects of L. reuteri have been proposed to be largely associated with the production of the broad-spectrum antimicrobial compound reuterin during anaerobic metabolism of glycerol.

Reuterin metabolises glycerol to hydroxypropionaldehyde (3-HPA), a low molecular weight, neutral, and soluble compound. This process is mediated by glycerol dehydratase and assisted by coenzyme B12 (vitamin B12). 3-HPA is further converted into acrolein, which exerts cytotoxic effects and inhibits the growth of Gram-negative bacilli — one proposed mechanism by which reuterin exerts its antibacterial effect.

Reuterin's main components are monomers, hydrates, and cyclodimers of 3-HPA, associated with glycerol metabolism. The antibacterial activity of reuterin is not destroyed by nuclease, protease, or lipase, giving it greater stability. It has broad-spectrum antimicrobial properties and can inhibit the growth of some Gram-positive bacteria, Gram-negative bacteria, and yeasts. Reuterin interacts with thiol groups in cells to inhibit the growth and reproduction of harmful bacteria.

Two-dimensional NMR studies with labelled glycerol demonstrated that L. reuteri JCM 1112 can convert glycerol to reuterin in vivo, substantiating the potential for reuterin production in the intestine. Given that glycerol is naturally present in faeces, the acquired ability to produce reuterin and cobalamin is considered an adaptive evolutionary response that likely contributes to the probiotic properties of L. reuteri.

L. reuteri possesses a unique cluster of 58 genes for the biosynthesis of reuterin and cobalamin (vitamin B12). This gene cluster has a lower GC content and appears to have been inserted into the conserved genome, suggesting it represents a genomic island acquired from an external source.

Reutericyclin

Reutericyclin is a tetramic acid derivative — specifically a 1,3-diacylpyrrolidine-2,4-dione compound — that can be produced by some L. reuteri strains. Sourdough-isolated strains such as LTH2584, TMW1.112, and TMW1.656 produce reutericyclin, a compound with antimicrobial activity against Gram-positive bacteria.

Other Organic Acids and Products

L. reuteri produces a variety of antimicrobial substances including hydrogen peroxide, lactic acid, reuterin, and reutericyclin. These substances display inhibitory activity against both Gram-positive and Gram-negative bacteria, yeasts, fungi, and parasites.

Cobalamin (Vitamin B12)

An important feature of L. reuteri is its capability to produce vitamin B12 (cobalamin). This is a rare feature among lactic acid bacteria; the only other species in this group reported to produce vitamin B12 is Lactobacillus coryniformis, but the vitamin levels in that species are reported to be 700 times lower compared to L. reuteri.

Mechanisms of Action

Modulation of the Gut Microbiome

L. reuteri has been reported to enrich intestinal microbial diversity and regulate the relative abundance of microorganisms, mainly manifesting as an increase in the numbers of beneficial genera and a decrease in harmful genera. Studies have shown that following administration of L. reuteri, the numbers of Lactobacillus and Bifidobacterium increased, whereas those of Escherichia coli, Staphylococcus, and Ruminococcus decreased. However, no consensus has been reached regarding its influence on microbial composition, which depends on heredity, environment, and strain specificity.

Intestinal Barrier Function

L. reuteri DSM 17938 and other strains upregulate the expression of E-cadherin and tight junction (TJ) proteins in infected intestinal epithelial cells (IECs) and competitively inhibit bacterial binding to TJs, thereby inhibiting infection-induced increases in intestinal permeability and protecting intestinal barrier function.

Immunomodulation

L. reuteri has been shown to stimulate or suppress innate immune responses by affecting cytokine production in macrophages, monocytes, and dendritic cells. The modulation of dendritic cells by L. reuteri has been shown to be mediated through the dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN), promoting development of regulatory T cells that produce high amounts of interleukin-10 (IL-10) and transforming growth factor-β (TGF-β).

L. reuteri strains may exert immunoregulatory effects in the human gut through controlling LPS-induced TNF-α and intestinal damage. Anti-inflammatory activity has been demonstrated in animal studies showing reduction of intestinal mucosal levels of pro-inflammatory cytokines including IL-8, IL-1α, interferon-α, and TNF-α in newborn rats with LPS-induced inflammation.

Tryptophan Metabolism and Indole Derivatives

Research has shown that L. reuteri promotes the differentiation of T cells into double-positive intraepithelial lymphocytes (DPIELs) by metabolising tryptophan to indole-3-lactic acid, which then activates the aryl hydrocarbon receptor (AhR) on CD4+ T cells, downregulating the transcription factor Thpok and inducing T cell differentiation into DPIELs.

L. reuteri interacts with host intestinal epithelial cells by regulating the intestinal flora, enhancing the intestinal mucosal barrier, regulating immune cells, inflammatory factors, chemokines, and antibodies, producing indole derivatives from tryptophan, secreting exopolysaccharide (EPS) and other bioactive factors, enhancing tight junctions, regulating gene expression, improving antioxidant activity, and further regulating the host immune system. As such, L. reuteri has the potential to be used as a new therapeutic or adjunctive therapy in atopic or autoimmune diseases.

Strain-Specific Immunological Profiles

L. reuteri strains can be divided into two functional subsets: immunosuppressive strains (ATCC PTA 6475 and ATCC PTA 5289) and immunostimulatory strains (ATCC 55730 and CF48-3A), each of which has potential therapeutic value in different contexts.

4. Scientific Evidence by Area of Use

4.1 Infantile Colic

Infantile colic is the area in which the evidence for L. reuteri DSM 17938 is strongest and most consistently replicated.

A meta-analysis published in PLOS ONE aimed to evaluate the efficacy and safety of L. reuteri DSM 17938 for infantile colic, performing a systematic literature retrieval of RCTs from PubMed, EMBASE, the Cochrane Library, and other databases. Six RCTs involving 423 infants with colic were included. The treatment increased colic treatment effectiveness at two weeks (RR = 2.84; 95% CI: 1.24–6.50; p = 0.014) and three weeks (RR = 2.33; 95% CI: 1.38–3.93; p = 0.002), though not at four weeks (RR = 1.41; 95% CI: 0.52–3.82; p = 0.498).

A separate meta-analysis (Sung et al., 2018, published in Pediatrics) found that the probiotic group was approximately twice as likely as the placebo group to experience treatment success at 7, 14, and 21 days (adjusted incidence ratios: 2.08 [95% CI 1.26–3.42], 1.98 [95% CI 1.46–2.70], and 1.71 [95% CI 1.35–2.15], respectively). In subgroup analysis, reductions in crying duration were observed in breastfed infants at all time points but not in formula-fed infants. There were no adverse events reported across the four included studies.

A network meta-analysis concluded that use of L. reuteri DSM 17938 represents the most evidence-based significant intervention to reduce the duration of crying time in infantile colic (WMD −51.3 min/day, 95% CI −72.2 to −30.5, P < 0.0001).

An RCT conducted in the United States (designed under FDA and NIH/NCCIH scrutiny) confirmed safety and tolerability of L. reuteri DSM 17938 in infants with colic, though its efficacy findings were more modest, with placebo response rates between 48% and 71%, comparable to those in some earlier European trials.

Evidence strength: Strong for breastfed infants using DSM 17938. Multiple RCTs and meta-analyses consistently demonstrate reduced crying duration. Evidence in formula-fed infants is weaker and less consistent.

4.2 Acute Infectious Diarrhea

L. reuteri has been studied across multiple digestive conditions, and research supports its application as an adjuvant strategy for diarrhea. It is well evidenced that L. reuteri can be recommended as an adjuvant strategy in therapeutic settings for diarrhea.

The role of L. reuteri in the effective treatment of infantile colic is clearly illustrated, and it has been widely used in the prevention and treatment of infantile reflux, functional constipation, and acute gastroenteritis.

L. reuteri DSM 17938 can live throughout the gastrointestinal tract and colonise in normal human gastric bodies, including the gastric antrum, duodenum, and ileum. In one study, colonisation required continuous supplementation for 7 days, with the highest colonisation rate reached at 21 days; after discontinuing supplementation, the colonisation rate decreased significantly at one week and was undetectable at two months.

Evidence strength: Moderate-to-good. RCTs support a reduction in the duration and severity of acute diarrhea in children, particularly using strain DSM 17938. Evidence in adults is more limited.

4.3 Helicobacter pylori Infection

Given the growing problem of antibiotic resistance, improving H. pylori treatment or providing adjunctive therapy is a clinical priority. A 2024 meta-analysis was conducted to evaluate whether L. reuteri could improve H. pylori eradication rate, reduce adverse events (AEs), and alleviate gastrointestinal symptoms, using data from RCTs retrieved from PubMed, Embase, and the Cochrane Library. Eight RCTs including 1,087 patients were included in this analysis. Patients treated with L. reuteri showed greater improvements in gastrointestinal symptoms (pooled mean difference: −2.43; 95% CI: −4.56 to −0.29; p = 0.03).

A separate 2025 meta-analysis of seven RCTs with a total of 518 patients found that patients who received L. reuteri added to their triple therapy showed a higher eradication rate than those with triple therapy alone (HR: 1.16, 95% CI [1.03, 1.31], p = 0.01). The pooled results showed that the addition of L. reuteri to triple therapy resulted in a significantly lower risk of taste distortion and diarrhea.

L. reuteri has a documented inhibitory effect on H. pylori through at least two distinct mechanisms. Certain strains coaggregate directly with H. pylori cells, preventing their adhesion to the gastric epithelium and facilitating clearance from the stomach.

Subgroup analysis by strain in one Lactobacillus meta-analysis showed that the pooled relative risk for H. pylori eradication was 1.18 (95% CI 1.03–1.34) specifically in the L. reuteri group.

Evidence strength: Moderate. Multiple RCTs and meta-analyses support L. reuteri as an adjunct to standard eradication therapy to modestly improve eradication rates and reduce GI side effects. It is not recommended as monotherapy for eradication. No clear consensus currently exists on when to administer probiotics as adjuvant therapy for H. pylori eradication, and the appropriate dosage and duration of treatment continue to be debated.

4.4 Necrotizing Enterocolitis (NEC) and Preterm Infants

A systematic review and meta-analysis updated in 2023 previously showed that L. reuteri DSM 17938 reduces necrotizing enterocolitis (NEC), late-onset sepsis (LOS), and time to full feeds (TFF) in preterm infants.

L. reuteri DSM 17938 attenuates experimental NEC by inducing tolerogenic intestinal dendritic cells (DCs) and regulatory T cells (Tregs), which in turn reduce the proliferation of pro-inflammatory lymphocytes and production of inflammatory cytokines via a mechanism that is dependent on TLR2.

Evidence strength: Moderate and improving. Updated meta-analyses support reductions in NEC and late-onset sepsis in preterm infants specifically with DSM 17938. Evidence quality is limited by heterogeneity across trials.

4.5 Bone Mineral Density

The importance of the gut microbiome for bone metabolism was first demonstrated in mice, but human data were lacking. A double-blind, placebo-controlled trial investigated whether L. reuteri ATCC PTA 6475 affects bone loss in older women with low BMD. Women aged 75 to 80 years with low BMD were randomised to receive 10¹⁰ CFU of L. reuteri 6475 daily or placebo. The predefined primary endpoint was relative change after 12 months in tibia total volumetric BMD (vBMD). Ninety women were included and 70 completed the study. L. reuteri 6475 reduced loss of total vBMD compared to placebo in the intention-to-treat analysis (−0.83%, 95% CI −1.47 to −0.19%).

Growing evidence from murine models has highlighted the benefit of probiotic bacteria in treating adverse bone pathology associated with numerous conditions, including oestrogen deficiency and type 1 diabetes. Results from this randomised, double-blind, placebo-controlled clinical trial demonstrated a beneficial effect of L. reuteri on human bone density.

A subsequent RCT (NCT05421871) specifically in early postmenopausal women did not demonstrate that L. reuteri 6475 prevented bone loss in that population, and current high-quality evidence does not support strain 6475 for preventing early postmenopausal bone loss.

Evidence strength: Preliminary. A single RCT showed attenuation of bone loss in elderly women (75–80 years) using strain 6475, but a trial in early postmenopausal women did not replicate this. Mechanistic data from animal studies are substantial, but human evidence remains limited to a small number of trials with narrow populations.

4.6 Cholesterol and Cardiovascular Risk Factors

L. reuteri has been exploited as a nutritional supplement in the context of cardiovascular risk reduction. A systematic review and meta-analysis hypothesised that L. reuteri consumption might improve significant cardiovascular disease risk factors, including blood pressure, blood lipids, and blood glucose. However, previous clinical studies had shown controversial results. PubMed, Embase, Scopus, the Cochrane Library, and Web of Science were searched for eligible RCTs published before May 2022.

Strain NCIMB 30242 has been the most studied for cholesterol outcomes. Clinical research with L. reuteri NCIMB 30242 in yoghurt formulation has demonstrated cholesterol-lowering efficacy in hypercholesterolaemic adults. This strain possesses a particularly active bile salt hydrolase (BSH) enzyme, which is thought to facilitate bile acid deconjugation, promoting faecal excretion of cholesterol-bound bile salts and reducing intestinal cholesterol re-absorption.

Evidence strength: Moderate but strain-specific. The strongest cholesterol-lowering evidence is for NCIMB 30242. Overall meta-analytic evidence for total cholesterol reduction exists, but effects on LDL cholesterol, blood pressure, and blood glucose have been inconsistent across trials.

4.7 Vaginal and Urogenital Health

Lactobacilli dominate the vaginal bacterial community in healthy women. One study showed that only 14 days of oral L. reuteri RC-14 administration could restore the normal vaginal flora in postmenopausal women. The relative abundance of lactobacilli is largely decreased in bacterial vaginosis (BV) patients. A total of 4 weeks of oral capsule consumption of two Lactobacilli strains including L. reuteri RC-14 increased the relative abundance of vaginal lactobacilli.

However, in pregnant women, 8 weeks of oral L. reuteri RC-14 treatment did not efficiently restore the normal vaginal microbiota, suggesting that the effectiveness of L. reuteri as a probiotic may depend on the clinical context.

A clinical study found that L. rhamnosus GR-1 and L. reuteri RC-14, taken orally, were helpful in vaginosis and bacterial vaginitis treatment and in relapse prevention, as they can re-establish the vaginal ecosystem.

However, in a crossover trial among pregnant women at high risk for preterm birth, L. rhamnosus GR-1 was detected in only 5% of women receiving oral probiotics, and L. reuteri RC-14 was not detected in any vaginal samples. Overall, vaginal colonisation of lactobacilli following oral administration was found to be low during pregnancy.

Evidence strength: Preliminary to moderate. Evidence supports a role for L. reuteri RC-14 (typically co-administered with L. rhamnosus GR-1) in restoring vaginal Lactobacillus flora in non-pregnant women with BV. Evidence in pregnant women is weaker, and actual vaginal colonisation following oral administration appears to be limited. Results across trials are mixed.

4.8 Oral Health

For oral health outcomes, most studies have used strains DSM 17938 and ATCC PTA 5289.

In a clinical study examining L. reuteri for periodontitis, probing depth improved by 35.8% and 68.3% of patients achieved ≥2 mm probing depth reduction versus 13.3% in controls (p < 0.001). Radiographic bone loss improved to mild Moffat grades in 66.7% of test patients versus 33.3% in controls (p < 0.001). The findings suggest that L. reuteri statistically significantly alleviates periodontitis by inhibiting inflammatory pathways, demonstrating clinically meaningful reductions in probing depth, clinical attachment level, and alveolar bone loss.

L. reuteri has been studied for the prevention and treatment of urogenital diseases, atopic disease, food hypersensitivity, and the prevention of dental caries.

Evidence strength: Preliminary to moderate. Small trials show promising results for periodontal health and caries prevention, but larger confirmatory trials are needed.

4.9 Vitamin D

A post-hoc analysis of a randomised controlled trial published in the Journal of Clinical Endocrinology and Metabolism (2013) demonstrated that supplementation with L. reuteri NCIMB 30242 increases mean circulating 25-hydroxyvitamin D levels. This finding was from a secondary analysis, not a pre-specified primary endpoint, and requires confirmation.

Evidence strength: Preliminary. Single post-hoc analysis with NCIMB 30242. Not replicated in prospective trials with vitamin D as a primary endpoint.

4.10 Atopic and Inflammatory Conditions

In animal models of atopic dermatitis, L. reuteri strains significantly reduced IgE levels, suppressed TSLP levels in skin tissue, and reduced IL-4 (a Th2-type cytokine). These findings are largely preclinical; robust human RCT evidence in atopic dermatitis remains limited.

While it is well evidenced that L. reuteri can be effective both as a prophylactic measure and as a preferred therapy for infantile colic, and can be recommended as an adjuvant strategy for diarrhea, constipation, and H. pylori infection, its application in functional abdominal pain, inflammatory bowel disease, diverticulitis, colorectal cancer, and liver diseases still needs further study.

5. Body Systems Associated

• Gastrointestinal system: Most extensively studied area; evidence in infantile colic (strong), acute diarrhea (moderate), H. pylori adjunctive therapy (moderate), constipation (preliminary), NEC prevention in preterm infants (moderate).
• Immune system: Dendritic cell and regulatory T cell modulation; cytokine regulation (IL-10, TGF-β, TNF-α); evidence predominantly preclinical and mechanistic.
• Skeletal system: Attenuation of age-related bone loss; evidence from one RCT in elderly women using strain 6475.
• Cardiovascular system: Cholesterol reduction (NCIMB 30242, moderate evidence); other cardiovascular risk factors inconsistent.
• Female urogenital system: Restoration of vaginal Lactobacillus flora in non-pregnant women with BV using RC-14; preliminary to moderate evidence.
• Oral cavity: Reduction of periodontal disease markers and caries risk; preliminary to moderate evidence.
• Endocrine system: Vitamin D elevation with NCIMB 30242 (preliminary, post-hoc only).

6. Dosage Forms and Reported Dosages

Dosages of L. reuteri across published studies have ranged from 1 × 10⁷ (ten million) colony-forming units (CFUs) to 1 × 10¹¹ (one hundred billion) CFUs per day, for durations of 5 days to 6 months.

• Infantile colic (DSM 17938): Daily doses in infant drops typically provide approximately 1 × 10⁸ CFU per day. In children and infants, dosages have usually been limited to 1 × 10⁹ CFUs daily.
• Bone mineral density (ATCC PTA 6475): In the pivotal RCT in older women, participants received 10¹⁰ colony-forming units of L. reuteri 6475 orally once daily for 12 months.
• Safety trial in healthy adults (DSM 17938): In a prospective, double-blind, placebo-controlled trial, forty healthy adults were randomised to a daily dose of 5 × 10⁸ CFUs for 2 months.
• Vaginal health (RC-14): In a crossover RCT in pregnant women, participants received two oral capsules per day each containing 5 × 10⁹ lactobacilli (L. rhamnosus GR-1 and L. reuteri RC-14 combined) for 2 months.
• H. pylori adjunctive therapy: Dosages varied across the eight RCTs included in the 2024 meta-analysis, generally using DSM 17938 strain preparations co-administered during standard eradication regimens.

Strain specificity is absolute — L. reuteri DSM 17938 and ATCC 55730 are different strains with different evidence bases and should not be substituted for one another.

7. Safety Considerations and Interactions

General Safety Profile

In a prospective, double-blind, placebo-controlled trial of daily L. reuteri DSM 17938 in healthy adults for 2 months, there were no severe adverse events (SAEs) and no significant differences in adverse events compared to placebo. LR was concluded to be safe and well tolerated in adults, without significant changes in immunologic markers.

The probiotic-treated group had a significantly higher fecal calprotectin level than the placebo group after 2 months (50 µg/g vs. 17 µg/g, p = 0.03), although values remained in the normal clinical range (0–162.9 µg/g). This small but significant increase may indicate some element of immune recognition at the intestinal level.

A number of studies conducted both in vivo and in vitro indicate that L. reuteri is safe for human consumption, even in large amounts.

Antibiotic Resistance Genes

In 2007, two plasmids carrying antibiotic resistance genes (tetracycline and lincomycin resistance) were removed from the parent strain ATCC 55730, resulting in the derivative strain DSM 17938, which is now the principal strain used in human clinical research and commercial products. As is the case for all other species of lactic acid bacteria, plasmids can be found in some strains of L. reuteri, and for strains intended for human use, the absence of transferable antibiotic resistance elements is considered a critical safety requirement.

Immunocompromised Patients

Lactobacillus species are generally not considered pathogenic; however, probiotics have been implicated in rare cases of endocarditis and bacteremia in immunocompromised patients.

Due to previous reports of Lactobacillus bacteremia, meningitis, endocarditis, and D-lactic acidosis (mostly in adults), one US RCT of L. reuteri in infants was designed with scrutiny by the FDA and the NIH/NCCIH.

Premature and Vulnerable Infants

In 2014, a fatal case of GI mucormycosis caused by Rhizopus oryzae was reported in a premature infant who had been given a probiotic to prevent necrotizing enterocolitis; testing revealed contamination of the probiotic product. None of the probiotic NEC prevention trials included in major meta-analyses or L. reuteri colic trials were conducted in the United States, most likely because of FDA approval requirements. This highlights the regulatory and safety complexities surrounding probiotic use in very premature or critically ill neonates.

Colonisation and Persistence

Colonisation with L. reuteri DSM 17938 required continuous supplementation for 7 days to establish, and the highest colonisation rate was reached at 21 days; after discontinuing supplementation, the colonisation rate decreased significantly at 1 week and was undetectable at 2 months. This transient colonisation profile suggests that supplementation must be ongoing to maintain potential effects.

Product Quality

Products should be verified to contain viable (live) bacteria at specified CFU counts, as product quality varies widely. Products deposited at biodepositories such as ATCC provide better quality assurance.

References

• Wikipedia — Limosilactobacillus reuteri
• ScienceDirect Topics — Lactobacillus reuteri (overview)
• Morita H et al. (2008). Comparative genome analysis of Lactobacillus reuteri and Lactobacillus fermentum reveal a genomic island for reuterin and cobalamin production. DNA Research. PubMed PMID 18487258.
• Duar RM et al. (2014). From Prediction to Function Using Evolutionary Genomics: Human-Specific Ecotypes of Lactobacillus reuteri Have Diverse Probiotic Functions. PMC4122935.
• Abuqwider J, Altamimi M, Mauriello G. (2022). Limosilactobacillus reuteri in Health and Disease. Microorganisms 10(3):522.
• Luo Z et al. (2023). Limosilactobacillus reuteri in immunomodulation: molecular mechanisms and potential applications. Frontiers in Immunology.
• Frontiers in Cellular and Infection Microbiology (2023). Lactobacillus reuteri in digestive system diseases: focus on clinical trials and mechanisms.
• Liu Y et al. (2015). The Efficacy and Safety of L. reuteri DSM 17938 for Infantile Colic: A Meta-Analysis of RCTs. PLOS ONE.
• Sung V et al. (2018). Lactobacillus reuteri to treat infant colic: a meta-analysis. Pediatrics. (Summary in Annals of Emergency Medicine).
• Vandenplas Y et al. (2017). Efficacy of L. reuteri DSM 17938 for infantile colic: Systematic review with network meta-analysis. PMC5758237.
• Fatheree NY et al. (2019). Lactobacillus reuteri for Infants with Colic: A Double-blind, Placebo-controlled, Randomized Clinical Trial. PMC6336100.
• Li M et al. (2024). Lactobacillus reuteri compared with placebo as an adjuvant in Helicobacter pylori eradication therapy: a meta-analysis of RCTs. PubMed PMID 38846173.
• Elkoumi O et al. (2025). Efficacy and Safety of Lactobacillus reuteri Supplementation Combined with Triple Therapy for Eradicating H. pylori: An Updated Meta-Analysis. PMC11777987.
• Nilsson AG et al. (2018). Lactobacillus reuteri reduces bone loss in older women with low bone mineral density: a randomized, placebo-controlled, double-blind, clinical trial. Journal of Internal Medicine. PubMed PMID 29926979.
• Mangalat N et al. (2012). Safety and Tolerability of Lactobacillus reuteri DSM 17938 and Effects on Biomarkers in Healthy Adults: Results from a Randomized Masked Trial. PMC3435331.
• Parvaneh K et al. (2019). Beneficial effects of Lactobacillus reuteri 6475 on bone density in male mice is dependent on lymphocytes. PMC6789011.
• Ang JY et al. (2023). Limosilactobacillus reuteri DSM 17938 as a probiotic in preterm infants: An updated systematic review with meta-analysis and trial sequential analysis. Journal of Parenteral and Enteral Nutrition.
• Mu Q et al. (2018). Role of Lactobacillus reuteri in Human Health and Diseases. Frontiers in Microbiology.
• Rigo-Adrover M et al. (2020). A Randomized Controlled Crossover Trial on Vaginal Colonization of Orally Administered Lactobacillus reuteri RC-14 and Rhamnosus GR-1 in Pregnant Women. PMC7230520.
• Vicariotto F et al. (2008). Efficacy of Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 in treatment and prevention of vaginoses and bacterial vaginitis relapses. PubMed PMID 18854803.
• Examine.com — Lactobacillus reuteri: benefits, dosage, and side effects.
• Buber E et al. (2020). The potential therapeutic role of Lactobacillus reuteri for treatment of inflammatory bowel disease. PMC7270012.
• Zhang Y et al. (2023). Limosilactobacillus reuteri Regulating Intestinal Function: A Review. Fermentation 9(1):19.
• Clinical Effects of Lactobacillus reuteri on Gingival Inflammation and Alveolar Bone Loss in Periodontitis. PMC12532032.