Introduction

Lactobacillus reuteri is a bacterium found in the digestive tracts of mammals, including humans, and in fermented foods. It is a member of the genus Lactobacillus, which comprises a large proportion of the bacteria that live on and in the human body. Lactic acid-producing bacteria, such as those in the Lactobacillus genus, are the most common type of bacteria used in probiotic supplements.[1] Furthermore, some online resources provide step-by-step instructions for at-home bulk production of yogurt with L. reuteri enrichment. (see also: 1, 2, 3).

L. reuteri has recently gained recent popularity due to emerging evidence (of varying quality) that suggests supplemental L. reuteri may provide or mediate the following effects:

  • Reduction in cholesterol levels: L. reuteri encapsulated in nanoparticles and added to food reduced LDL cholesterol by 12 percent and total cholesterol by 9 percent among adults with high cholesterol.[2]

  • Strengthening of the gut barrier: L. reuteri supplementation induced cycles of short-chain fatty acid production in gut microbes, improving intestinal permeability (i.e., leaky gut).[3]

  • Increase in oxytocin and acceleration of wound healing L. reuteri supplementation in mice accelerated wound healing due to an increase in oxytocin (known as the "cuddle hormone").[4]

  • Increase in serum testosterone and testicular size: L. reuteri supplementation increased serum testosterone in mice; however, this effect was small and its relevance for humans is not well understood.[5] [6]

  • Reduction in the development of allergies: L. reuteri supplementation from week 36 of pregnancy and during the first year of an infant's life significantly decreased eczema and allergic responsiveness (Th2 cell-mediated) overall.[7]

  • Protection from pathogens: L. reuteri supplementation may increase the eradication rate of Heliobacter pylori, a stomach bacterium that can cause ulcers.[8] Additionally, some evidence suggests supplementation may reduce diarrhea caused by gastroenteritis in children.[9]

  • Reduced risk of death in preterm infants: Lactobacillus probiotic supplementation significantly reduced the risk of severe necrotizing enterocolitis by 42 percent and death by 65 percent in preterm infants.[10]

This article will discuss the safety and efficacy of L. reuteri supplementation for gut and whole-body health rather than yogurt production.

L. reuteri is a probiotic that provides nutrition and protection from pathogens.

The human body has been described as a superorganism, an ecosystem composed of human cells, microbial cells, viruses, and inputs from the environment. The body can be divided into multiple microbiomes including those of the skin, respiratory tract, and urogenital tract;[11] however, the gastrointestinal microbiome is the most-studied and may have the greatest influence on overall human health.

Probiotics are widely-defined as live bacteria that produce health effects when consumed at a sufficient dosage. These health benefits are related to probiotics' ability to 1) modulate the gut microbiome, promoting the growth of beneficial bacteria, archaea, and fungi and preventing the growth of pathogenic microbes; 2) improve barrier function by tightening the connections between intestinal cells and maintaining an effective mucus layer between gut cells and microbes; and 3) communicate with the immune system, activating regulatory and helper T cells, and balancing the ratio of pro-inflammatory and anti-inflammatory cytokines.[12]

Due to their ability to produce lactic acid, Lactobacillus bacteria increase the acidity of the intestinal contents. While many native, beneficial members of the microbiome are resistant to stomach and intestinal acidity, pathogens are less able to cope with acidity.

L. reuteri produces an antimicrobial compound called reuterin.

In addition to its production of acidic compounds, L. reuteri suppresses the growth of pathogenic microbes by producing a broad-spectrum antimicrobial compound called reuterin.[13] Reuterin is such a broad-ranging antibacterial compound that it inhibits the growth of most commensal bacteria outside of the Lactobacillus genera.[13] It is unclear why certain bacteria are more resistant to reuterin than others. Reuterin is produced by most known strains of L. reuteri and is also effective in inhibiting the growth of molds.[14]

L. reuteri produces some forms of vitamin B12.

In addition to the infection prevention benefits to the host, L. reuteri produces vitamin B12 (also called cobalamin), an essential nutrient that acts as a cofactor in the synthesis of DNA and in the metabolism of dietary fat and protein.[15] The human genome does not contain the genes necessary to produce vitamin B12, so it must be obtained through diet. Cobalamin is also an essential nutrient for bacterial metabolism; however, most bacteria lack the genes to produce and must obtain it from the environment as well. L. retueri was the first lactic acid bacteria found to produce vitamin B12.[16] As Lactobacillus bacteria are often used in yogurt making, food producers looking to fortify their fermented products with vitamin B12 may findL. reuerti to be a useful food additive.[16] The authors of one report, who used the bacteria to produce fortified soy yogurt, identified L. reuteri as a useful food additive for vegetarians and older adults who have increased dietary need for vitamin B12.[17]

Other sources find that the version of cobalamin produced by L. reuteri is structurally different from the active vitamin form and is not well-absorbed. A study in mice revealed that L. reuteri supplementation at a concentration of 10 million colony-forming units (CFU) (i.e., the unit used to measure the concentration of bacteria in a dose of probiotics) prevented the effects of vitamin B12 deficiency in mice fed a vitamin B12-deficient diet.[18] These results have not been replicated in humans and warrant future research.

L. reuteri reduces gut leakiness and strengthens the intestinal barrier.

The gut barrier is composed of multiple layers, including a layer of intestinal epithelial (i.e., skin-like) cells with connective tissue called the lamina propria beneath. This epithelial layer secretes mucus that forms an additional barrier between the gut cells and the stream of food and microbes passing through the small intestine. Scattered throughout the lamina propria are structures called Peyer's patches, which perform multiple immune functions such as producing white blood cells including macrophages, T cells, and B cells. These immune cells monitor the gut environment in order to regulate the number and types of microbes in the intestines.[19]

Intestinal cells are connected to each other by structures called tight junctions. These tight junctions prevent bacteria from penetrating between cells in the intestinal wall and entering the bloodstream. A high-fat diet has been shown to increase gut leakiness, although different types of fat tend to have different effects on the gut barrier, with short-chain fatty acids increasing gut barrier integrity and long-chain fatty acids increasing leakiness.[20] Long-chain fatty acids include saturated fats like palmitic acid and stearic acid (found in a variety of plant and animal foods) and unsaturated fats like the omega-6 fat linoleic acid (found mostly in vegetable oils). These fats activate immune cells in the gut mucosa, increasing inflammation and down-regulating the production of tight junction proteins, thereby increasing gut leakiness. High-fat diets also increase the secretion of bile acids, which are needed to emulsify fats so they can be absorbed. Increased bile acid production also down-regulates the production of tight junction proteins, increasing intestinal permeability.[20]

Short-chain fatty acids such as acetate, propionate, and butyrate, on the other hand, increase gut barrier integrity due to a number of physiological mechanisms. This increase is partly due to the up-regulation of tight junction proteins. Butyrate, specifically, is the preferred source of energy for intestinal cells and increases the rate of tight junction assembly.[21] In one study of mice consuming a high-fat diet, supplementation with 100 million CFU of L. reuteri strain FN041 for four weeks significantly reduced weight gain and cholesterol levels and improved gut barrier integrity. The researchers used a test called a fluorescein isothiocyanate-dextran (FD4) assay to measure the permeability of the gut barrier and found that L. reuteri supplementation reduced the gut leakiness induced by the high-fat diet. The mice that received L. reuteri also had lower blood levels of bacterial endotoxin and tumor necrosis factor (TNF)-alpha, a pro-inflammatory cytokine.[3]

The authors of the report found that improvements in the gut barrier were dependent on the development of an oscillatory cycle of metabolic behavior. Mice consuming a high-fat diet without the L. reuteri probiotic had a reduction in metabolic activity of the gut microbiota at 2:00 PM and 8:00 PM, while the microbiota of mice who were supplemented with L. reuteri were more metabolically active at 2:00 PM, 8:00 PM, and 8:00 AM. L. reuteri supplementation increased the colonic concentration of lactate, propionate, and butyrate and also increased colonic expression of the tight junction protein occludin.[3] These results demonstrate the potent ability of probiotics to ameliorate some of the deleterious effects of a Western diet. However, it is important to note that mice have very different nutritional needs than humans, so additional clinical research is needed to confirm the relevance of these results.

In addition to reducing the absorption of toxins, an increase in gut barrier integrity reduces the risk of infection. In one small clinical trial, participants took a supplement containing 400 million CFU of L. reuteri strain ATCC 55730 for 28 days. The investigators collected biopsies from the stomach or small intestine before and after supplementation. Probiotic supplementation caused a significant increase in the number of intestinal B cells and CD4 positive cells, both of which facilitate the antibody response to infection. This increase in CD4 positive cells is in line with previous studies of L. reuteri supplementation in poultry and rats reporting improved gut barrier function and decreased risk of Salmonella infection. However, supplementation did not alter the number of white blood cells or inflammatory cytokines in blood circulation.[22] This highlights the importance of using research methods that sample the gut directly, such as the biopsies used in the study, and not just blood samples. Unfortunately, biopsies and other direct sampling can often be too invasive and expensive to do in human trials. This dilemma is important to consider when extrapolating data collected in scientific studies to make recommendations for probiotic use by individuals.

Metabolic effects of L. reuteri

L. reuteri lowers cholesterol and increases vitamin D absorption.

Cholesterol is a lipid molecule that is used to build and repair cells and serves as a precursor for the production of steroid hormones, vitamin D, and bile acids. Bile acids are produced by the liver and secreted into the digestive tract, where they emulsify dietary fats. Bile acids are reabsorbed by the small intestine along with dietary cholesterol, fats, and fat-soluble vitamins such as vitamins A, D, E, and K. Cholesterol is recycled through this route between the liver and intestines.[23]

Bacteria in the gut microbiota play significant roles in the recycling of bile acids and cholesterol. When bile acids are released from the liver, they are conjugated (i.e., connected) to amino acids that make them more soluble in water. In this state, they are called bile acid salts. Some bacteria produce enzymes that break the bonds between bile acids and their conjugated amino acids, called bile salt hydrolases. These deconjugated bile acids are less able to be reabsorbed in the intestine, thus increasing the loss of bile and of cholesterol in feces.[24] This decreased reabsorption and increased loss of bile acids necessitates the production of more bile acids in the liver, decreasing the overall pool of cholesterol available in the body, which may be beneficial in managing high cholesterol.[25]

A growing number of studies have demonstrated the ability of some probiotics with bile salt hydrolase activity to decrease LDL-cholesterol levels in those with high cholesterol, including the Lactobacillus genera.[25] One report from 1998 demonstrates the effects of probiotic supplementation on cholesterol levels in mice fed a cholesterol-raising diet. They fed mice either a standard diet or a diet enriched with saturated fat from heavy cream for seven days. The high saturated fat diet increased total cholesterol by 1.9 times, HDL cholesterol by 2.1 times, LDL cholesterol by 1.6 times, and triglycerides by 1.1 times compared to the standard diet. Then the investigators treated mice with 10,000 CFU of L. reuteri CRL 1098 for seven days. L. reuteri supplementation reduced cholesterol levels by 38 percent in mice eating a high saturated fat diet, bringing their cholesterol levels down to the same level as mice eating a standard diet. Mice on the high saturated fat diet with L. reuteri also had a 40 percent reduction in triglycerides and a 20 percent increase in the ratio of HDL to LDL. The authors did not measure bile acid concentrations but speculated that the ability of L. reuteri supplementation to reduce blood lipids is due to the microbes' ability to deconjugate bile acids.[26]

The same group of researchers repeated their experiment in a later study published in 2000, but this time they supplemented mice with L. reuteri prior to feeding them a cholesterol-raising diet. They gave mice a standard chow diet and assigned them to one of three treatment groups. Group one consumed water supplemented with 10,000 CFU of L. reuteri strain CRL 1098 for seven days, group two consumed water supplemented with non-fat milk for seven days, and group three consumed normal water. Next, the researchers fed groups one and two the same saturated fat-supplemented diet they used in their 1998 experiments for seven days. Group three, the control group, remained on the standard diet for an additional seven days.

The high saturated fat diet increased total cholesterol by 1.8 times, triglycerides by 1.6 times, and decreased the ratio of HDL to LDL by 1.3 times in mice fed non-fat milk compared to the control group drinking plain water. L. reuteri supplementation decreased total cholesterol by 20 percent and triglycerides by 33 percent compared with group two, which received milk without L. reuteri. The authors concluded that prophylactic probiotic supplementation reduced the cholesterol-raising effects of a high-saturated fat diet. These results demonstrate that L. reuteri persists in the digestive tract and influences metabolism after supplementation had ended. L. reuteri has a high resistance to stomach acid and bile acids, which allows for better colonization in the digestive tract and improves its function as a probiotic.[27]

Other recent studies in humans have reached similar conclusions about the cholesterol-lowering effects of L. reuteri. In one double-blind, randomized, controlled trial, researchers asked participants with high cholesterol to consume yogurt containing 5 billion CFU of microencapsulated L. reuteri NCIMB 30242 or placebo yogurt. Participants consumed the yogurt twice daily for six weeks. The authors reported that participants in the intervention group experienced a nine percent reduction in LDL cholesterol and a five percent reduction in total cholesterol.[2]

In the latter study, the same group of researchers investigated the cholesterol-lowering effects of L. reuteri encapsulated in microparticles and added to food. This mode of probiotic delivery protects the bacteria from harsh stomach conditions and increases their delivery to the small intestine. For this experiment, the researchers asked participants with high cholesterol levels to consume a supplement containing 3 billion CFU of L. reuteri strain NCIMB 30242 or a placebo for nine weeks. Participants who consumed the probiotic supplement experienced a 12 percent reduction in LDL cholesterol and a nine percent reduction in total cholesterol.[2]

There is some concern that the reduced absorption of bile acids following L. reuteri supplementation may also reduce the absorption of fat-soluble vitamins. However, upon completing a secondary analysis of their data, the researchers found no differences in serum levels of vitamin A, vitamin E, or beta-carotene between the probiotic and control groups. Interestingly, they discovered that participants had significantly higher levels of serum vitamin D following nine weeks of L. reuteri supplementation. The reason for this increase in vitamin D is unclear; however, the authors hypothesized that L. reuteri probiotics, due to their production of lactic acid, increase intestinal acidity acid, which improves vitamin D absorption. Another theory is that L. reuteri supplementation may increase the body's production of vitamin D.[28]

L. reuteri supplementation reduces hemoglobin A1C and other markers of diabetes.

Previous research in animals and humans has demonstrated the efficacy of probiotics in the improvement of type 2 diabetes symptoms. This beneficial effect is mainly attributed to probiotics' ability to strengthen the gut barrier and attenuate leaky gut. This strengthened gut barrier reduces whole-body inflammation, improving insulin function and increasing insulin sensitivity.[29]

To determine the effects of L. reuteri supplementation on metabolic health, authors of one report fed rats a probiotic supplement with 1 billion CFU of L. reuteri strain GMNL-263 for 14 weeks or a placebo. When challenged with a high fructose diet, rats in the placebo group experienced insulin resistance, fatty liver, and increased inflammation; however, supplementation with L. reuteri significantly reduced these effects in the probiotic group.[30] Authors of another study in rats reported the ability of the same strain to reduce hemoglobin A1C and blood glucose levels after 28 days of supplementation.[31]

Subsequent to the studies in mice, the same group of researchers conducted a randomized, double-blind, controlled trial in humans. Participants with type 2 diabetes consumed either 4 billion CFU of live L. reuteri strain ARD-1, 20 billion CFU of heat-killed L. reuteri strain ARD-3, or a placebo for six months. While the definition of probiotics specifies that they are live organisms, there may be safety concerns for immunocompromised individuals, who may develop pathogen overgrowth. Live supplements are also more difficult to standardize and store, making heat-killed supplements an attractive choice if they demonstrate efficacy. Previous research by this group showed that live and heat-killed organisms had similar effects on metabolic function in rats, supporting the use of heat-killed supplements in this study.[32] Participants in the live probiotic group had a statistically significant reduction in hemoglobin A1C compared to the heat-killed probiotic and placebo groups following six months of supplementation, but not three months. Live probiotic supplementation also resulted in a trend toward decreased cholesterol levels. In the heat-killed probiotic group, participants did not experience changes in diabetic markers or cholesterol, but did experience a statistically significant reduction in systolic blood pressure (i.e., the top number in standard blood pressure notation) and average blood pressure.[33] It is important to note that the beneficial effects of supplementation on hemoglobin A1C were only present following supplementation for six months, which is a longer treatment duration than most other L. reuteri probiotic trials.

Another randomized, double-blind, placebo-controlled trial in adults with type 2 diabetes who were receiving insulin therapy reported conflicting results. The researchers gave participants either a low dose (100 million CFU) or high dose (10 billion CFU) of L. reuteri strain DSM 17938 or a placebo for 12 weeks. Although participants in the high dose group did experience an increase in insulin sensitivity, this relationship was not statistically significant. Participants in the low dose group did not experience reductions in hemoglobin A1C or other markers of diabetes. After further statistical analysis, the authors found that participants with the greatest increase in insulin sensitivity started the trial with a more diverse microbiota. They suggested that variation in microbiota composition may determine an individual's response to taking a probiotic.[34] A lack of harmonization of research methods (e.g., dose, duration, strain) across trials likely contributes to the inconsistencies that exist in the current body of L. reuteri research; therefore, additional research is needed to support the use of L. reuteri probiotics in treating type 2 diabetes.

L. reuteri as a probiotic in child development

Maternal diet may increase the prevalence of L. reuteri in breast milk.

Breast milk is not only a source of nutrition for infants, but it is also an important source of bioactive factors that support the development of a healthy microbiome. Bacteria is transferred from the mother's skin to the infant during feeding, but is also found in breast milk due to microbial colonization of maternal milk ducts. Lactobacillus bacteria are one of the main colonizers of breast milk and, subsequently, the infant digestive tract.[35]

Multiple strains of L. reuteri have been isolated from human breast milk, where they serve to improve infant nutrition, educate the immune system, protect the infant from pathogens, and guide the development of a healthy digestive tract.[36] In one study, researchers measured the concentration of L. reuteri in breast milk from 220 mothers from rural and urban areas in seven countries six to 32 days after delivery. Overall, 15 percent of mothers had detectable L. reuteri in their milk. Rates were highest in rural Japan and Sweden, with up to 50 percent of mothers presenting with L. reuteri in their breast milk. Mothers from urban areas of South Africa, Israel, and Denmark had the lowest rates of L. reuteri. There was no statistically significant difference between rural and urban mothers. The authors speculated that Japanese women had the highest levels of L. reuteri in their breast milk due to the consumption of probiotics from fermented foods that are an important part of the Japanese diet.[37] This suggests that diet may directly modulate the composition microbes that colonize the milk ducts and, ultimately, the infant digestive tract.

L. reuteri protects preterm infants from necrotizing enterocolitis and improves nutrition.

Breast milk-derived probiotics offer substantial developmental benefits. Preterm neonates, those born before 37 weeks of gestation, are at increased risk of nutritional deficiencies that stunt growth and development. Because of the underdevelopment of the digestive tract and immune system, these infants are also at an increased risk of intestinal infections like necrotizing enterocolitis, which is a disease primarily affecting preterm infants. In necrotizing enterocolitis, bacteria invade the intestinal wall, causing inflammation that damages the gut. Necrotizing enterocolitis may progress to sepsis and even death, prompting researchers to develop strategies for prevention and treatment. With their ability to strengthen the gut barrier, compete with pathogens, and strengthen the host's immune response, probiotics may be one such treatment.[38]

Candida yeasts are the most common cause of fungal infections. The species Candida albicans is a friendly fungus found in the guts of most healthy people; however, in susceptible individuals, it is an opportunistic pathogen.[39] Once Candida has breached the gut barrier and entered circulation, a state called candidemia, it may cause organ dysfunction and death. In individuals with a healthy gut microbiota, native bacteria out-compete Candida for colonization of the gut wall, preventing Candida from crossing the gut barrier. In mice fed antibiotics, Candida associates freely with the gut wall, passing easily into circulation and initiating infection. Preterm infants who have yet to establish a healthy microbiota are at a similar risk of candidemia as those following antibiotic treatment.[40]

To determine the effects of probiotic supplementation in the prevention of candidemia, late-onset sepsis, and neurological deficits, researchers assigned a group of 249 preterm infants to one of three groups. Infants in group one consumed five drops of a supplement containing 100 million CFU of L. reuteri strain ATCC 55730. Infants in group two consumed 6 billion CFU of L. rhamnosus strain ATCC 53103. Infants in group three consumed no probiotics. The investigators began supplementation within 72 hours of birth and continued supplementation for six weeks or until discharged from the neonatal intensive care unit.

The authors reported that while there was no significant difference in candidemia between the three groups, probiotic supplementation resulted in significantly less Candida colonization. Supplementation with L. reuteri significantly reduced the length of parenteral nutrition (where all nutrients are delivered intravenously) needed and the length of hospitalization compared to supplementation with L. rhamnosus or no probiotic supplementation. This effect was greatest in infants with the lowest birth weights. In those infants who developed a Candida infection that required antimycotic or antibiotic treatment, probiotic supplementation with either L. reuteri or L. rhamnosus decreased the number of days of treatment required compared to no probiotics. Finally, 47 infants out of 249 developed neurological deficits. Compared to those in both probiotic groups, infants who did not receive probiotics had a statistically significant higher incidence of suboptimal neurological assessment scores at one year of age.

The authors stated that their study demonstrates the beneficial effects of L. reuteri supplementation on multiple outcomes related to gut function, including greater food tolerance, improved bowel habits, and quicker stomach emptying, which then reduces episodes of regurgitation. They noted that, while both probiotic treatments performed better than no probiotic treatment, these beneficial effects are greater with L. reuteri supplementation than with L. rhamnosus supplementation. They speculated this may be due to lower rates of colonization of L. rhamnosus compared to L. reuteri, especially in the infants with the lowest birth weights. Overall, they concluded that probiotic use in preterm infants is safe and improves gastrointestinal symptoms, food tolerance, and neurological outcomes at one year of age.[41]

One group of researchers performed a randomized control trial of prophylactic L. reuteri supplementation with 750 preterm infants. Infants began the study within 48 hours of birth and consumed either five drops of a probiotic liquid containing 100 million CFU of L. reuteri DSM 17938 or a placebo daily for the duration of their hospital stay. Probiotic supplementation reduced rates of pneumonia by three percent and enterocolitis by 40 percent, although these relationships were not statistically significant. Infants in the probiotic group had fewer episodes of feeding intolerance (10 percent in the probiotic group, 17 percent in the placebo group) and shorter duration of hospital care (32 days in the probiotic group, 37 days in the placebo group). Rates of death and other hospital-acquired infections were similar between groups. The authors speculated that their lack of significant results may have been the result of too few participants or a probiotic dose that was not strong enough for proper colonization of the gut.[42]

Authors of a 2016 meta-analysis, a type of review that combines and analyzes data from multiple trials, aimed to assess the effects of L. reuteri strain DSM 17938 in preterm neonates. They included six randomized controlled trials with more than 1,700 participants. Supplementation with L. reuteri DSM 17938 significantly reduced the average time for infants to adequately feed by one day, length of hospitalization by almost 11 days, and risk of sepsis by 66 percent. The risk of severe necrotizing enterocolitis was reduced by 69 percent and risk of death was reduced by 79 percent with supplementation, although these relationships were not statistically significant. In all studies, L. reuteri supplementation was safe and produced no adverse effects. The authors conclude that L. reuteri supplementation has the potential to reduce the risk of necrotizing enterocolitis and late-onset sepsis while improving eating and nutrition in preterm infants, although larger randomized clinical trials are needed to confirm these findings.[43]

The Cochrane Library, an organization that produces high-quality systematic reviews and meta-analyses of medical research, conducted a meta-analysis of clinical trials to compare the safety and efficacy of probiotic treatments in the prevention of severe necrotizing enterocolitis and sepsis in preterm infants. The authors included 24 trials in their analysis and found that probiotic supplementation significantly reduced the risk of severe necrotizing enterocolitis by 42 percent and death by 65 percent but did not reduce the risk of sepsis. They reported that probiotic treatments containing either Lactobacillus alone or in combination with Bifidobacterium were effective. They concluded that probiotic supplementation prevents severe necrotizing enterocolitis and death from all causes in preterm infants and that these results strongly support a change in the clinical care of preterm infants.[10]

L. reuteri supplementation reduces symptoms of colic in infants.

Although far less dangerous than necrotizing enterocolitis, colic is another disorder affecting the digestive tract in infants. Colic is defined as excessive and inconsolable crying without an identifiable cause and is common in infants in the first three months of life. The cause of colic is unknown, but disturbances in the intestinal microbiota that cause gut motor dysfunction and excess gas production may contribute to colicky behavior.[44] Some research reports an increased presence of hydrogen gas produced by gram-negative bacteria, lower rates of colonization of Lactobacilli, and increased Escherichia coli in infants with colic.[45]

To determine the effects of L. reuteri supplementation on symptoms of colic, one group of researchers performed a randomized, double-blind, controlled trial with 46 infants. The investigators assigned infants to receive 100 million CFU of L. reuteri DSM 17938 or a placebo for 21 days. Parents completed questionnaires about their infant's behavior and collected a stool sample from their infant for microbiome analysis. L. reuteri supplementation significantly reduced the average amount of time the infants cried compared to placebo. Infants in the L. reuteri group exhibited a significant increase in fecal Lactobacilli and a decrease in fecal E. coli. The authors concluded that L. reuteri supplementation reduced symptoms of colic and was well-tolerated with no adverse effects.[44]

While some research has reported benefits in infants with colic, other evidence is conflicting. A 2018 meta-analysis including data from four double-blind randomized controlled trials aimed to determine the effects of L. reuteri supplementation on time spent crying or fussing in infants with colic. L. reuteri supplementation reduced time spent crying or fussing compared to placebo, and infants supplemented with L. reuteri were twice as likely to experience treatment success. While these results were statistically significant for breastfed infants, they were not significant in formula-fed infants. The authors concluded that L. reuteri supplementation is effective and should be recommended for breastfed infants with colic but that the evidence is inconclusive for formula-fed infants.

Supplementation with L. reuteri before or during a gastrointestinal infection reduces diarrhea in children.

Infections causing diarrhea, including rotavirus, are among the most common ailments affecting children worldwide,[46] prompting many to investigate the benefits of probiotics for these illnesses. In one study, researchers administeredL. reuteri strains isolated from breast milk to infants between 3 and 36 months of age hospitalized with diarrhea caused by rotavirus and other pathogens. Consumption of L. reuteri at a concentration of 10 billion CFU or 100 billion CFU for up to five days reduced the duration of watery diarrhea. There was no difference between the 10 and 100 billion CFU doses.[47]

In a subsequent study, the authors tested the efficacy of a lower dose of the probiotic in the same population. Compared to a placebo, a dose of 10 million CFU ended watery diarrhea sooner; however, a dose of 10 billion CFU provided an even quicker recovery, leading the authors to conclude that supplementation has a dose-dependent effect.[48]

In a community-based study, investigators fed children a probiotic beverage containing L. reuteri or a control beverage for 14 weeks. The authors reported a reduction in the number of children who developed diarrhea in the probiotic group (77 children out of 120) compared to the control group (90 children out of 119), demonstrating the efficacy of daily probiotic supplementation in the prevention of childhood diarrhea.[46]

A second study of daily supplementation confirmed these results. Researchers administered a probiotic supplement containing 100 million CFU of L. reuteri DSM 17938 to children aged 3 to 36 months for three months with an additional three-month follow-up. Supplementation with the probiotic significantly reduced the number of cases of diarrhea and respiratory illness after three months of supplementation. This effect persisted for an additional three months following the end of supplementation, establishing a long-lasting effect on the body. The authors also reported a significant reduction in the number of doctor visits, antibiotic use, absenteeism from school, and parental absenteeism from work.[49]

A later review of eight randomized controlled trials confirmed the beneficial effects of L. reuteri supplementation in reducing the duration of diarrhea and preventing the occurrence of community-acquired diarrheal illness.[50]

Conclusions

Lactobacillus reuteri has demonstrated a plethora of unique biological effects across a wide range of clinical and non-clinical research that seemingly converge on a few key mechanisms, including strengthening the gut barrier and immune system, improving metabolism, and protecting infants from digestive diseases, among others. In future research, probiotic supplementation may be guided by more advanced algorithms that are able to tailor treatments to individuals. These cocktails of probiotics and prebiotics may be used to eradicate specific harmful species while encouraging helpful bacteria to grow. L. reuteri is an interesting microbe, not only for its discrete effects shown across a wide variety of studies but also due to its growing popularity for home-based culturing yogurt.

L. Reuteri FAQs

Q: What dosage and strain of L. reuteri are the most likely to exhibit effects in humans?

A: Because research into the use of probiotics is still quite new, there are no established clinical dosage recommendations for L. reuteri or most other probiotics. Please see the summary chart of dosages and effects we've put together for this page, below.

Q: Are the probiotic supplements at the store viable?

A: Because most probiotic supplements are sold at room temperature, many consumers worry that the bacteria have died before they even purchase the supplement. Because probiotic supplements are not regulated in the United States, it is often impossible to be sure of their quality. There is also a lack of research investigating the stability of probiotics at room temperature. One study found that Lactobacillus and Bifidobacterium species used as probiotics do maintain their viability at room temperature if they are dehydrated properly during processing.[51]

Table 1. Summary of dosages of Lactobacillus reuteri and correspondent effects on health

Table 1. Summary of dosages of Lactobacillus reuteri and correspondent effects on health

  1. ^ Shaping the Future of Probiotics and Prebiotics Trends in Microbiology 29, no. 8 (August 2021): 667–85. https://doi.org/10.1016/j.tim.2021.01.003.
  2. ^ a   b   c Cholesterol-lowering efficacy of a microencapsulated bile salt hydrolase-activeLactobacillus reuteriNCIMB 30242 yoghurt formulation in hypercholesterolaemic adults British Journal of Nutrition 107, no. 10 (November 2011): 1505–13. https://doi.org/10.1017/s0007114511004703.
  3. ^ a   b   c Lactobacillus reuteri improves gut barrier function and affects diurnal variation of the gut microbiota in mice fed a high-fat diet Food & Function 10, no. 8 (2019): 4705–15. https://doi.org/10.1039/c9fo00417c.
  4. ^ Microbial Symbionts Accelerate Wound Healing via the Neuropeptide Hormone Oxytocin PLoS ONE Edited by Silvana Gaetani. 8, no. 10 (October 2013): e78898. https://doi.org/10.1371/journal.pone.0078898.
  5. ^ Characterization of the anti-inflammatory Lactobacillus reuteri BM36301 and its probiotic benefits on aged mice BMC Microbiology 16, no. 1 (April 2016). https://doi.org/10.1186/s12866-016-0686-7.
  6. ^ Probiotic Microbes Sustain Youthful Serum Testosterone Levels and Testicular Size in Aging Mice PLoS ONE Edited by Stefan Schlatt. 9, no. 1 (January 2014): e84877. https://doi.org/10.1371/journal.pone.0084877.
  7. ^ DOI: doi.org/10.1111/cea.12082
  8. ^ Lactobacillus reuteri Strain Combination In Helicobacter pylori Infection Journal of Clinical Gastroenterology 48, no. 5 (May 2014): 407–13. https://doi.org/10.1097/mcg.0000000000000007.
  9. ^ Lactobacillus reuteri DSM 17938 shortens acute infectious diarrhea in a pediatric outpatient setting Jornal de Pediatria 91, no. 4 (July 2015): 392–96. https://doi.org/10.1016/j.jped.2014.10.009.
  10. ^ a   b DOI: 10.1002/14651858.CD005496.pub5/full
  11. ^ “Structure, Function and Diversity of the Healthy Human Microbiome.” Nature 486, no. 7402 (June 2012): 207–14. https://doi.org/10.1038/nature11234.
  12. ^ Probiotics, gut microbiota and health Médecine et Maladies Infectieuses 44, no. 1 (January 2014): 1–8. https://doi.org/10.1016/j.medmal.2013.10.002.
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