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 most of the bacteria that live on and in the human body. Lactic acid-producing bacteria, such as those in the Lactobacillus genus, are commonly 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 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 poorly 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.
"The human body is a superorganism, an ecosystem composed of human cells, microbial cells, viruses, and environmental inputs." Click To Tweet
The human body is a superorganism, an ecosystem composed of human cells, microbial cells, viruses, and environmental inputs. It contains 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 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 microbiome members resist stomach and intestinal acidity, pathogens are typically less acid-resistant.
"L. reuteri suppresses the growth of pathogenic microbes by producing a broad-spectrum antimicrobial compound called reuterin." Click To Tweet
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 non-Lactobacillus commensal bacteria[13] and many molds.[14] It is unclear why certain bacteria are more resistant to reuterin than others. Most known strains of L produce Reuterin. reuteri.
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 acquired via the diet. Cobalamin is also an essential nutrient for bacterial metabolism; however, most bacteria lack the genes to produce and must also obtain it from the environment. 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 helpful food additive.[16] The authors of one report, who used the bacteria to produce fortified soy yogurt, identified L. reuteri as a helpful food additive for vegetarians and older adults with 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 poorly 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 bacterial concentrations 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.
The gut barrier comprises 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, forming 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 to regulate the number and types of microbes in the intestines.[19]
Intestinal cells connect via 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 increases gut leakiness, although different types of fat tend to elicit differential 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 chiefly 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]
On the other hand, short-chain fatty acids such as acetate, propionate, and butyrate increase gut barrier integrity due to many physiological mechanisms. This increase is partly due to the up-regulation of tight junction proteins. Butyrate, specifically, is the preferred energy source 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 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 report's authors found that improvements in the gut barrier depended on developing an oscillatory cycle of metabolic behavior. Mice consuming a high-fat diet without the L. reuteri probiotic exhibited reduced gut microbiota metabolic activity at 2:00 p.m. and 8:00 p.m., while the microbiota of mice supplemented with L. reuteri were more metabolically active at 2:00 p.m., 8:00 p.m., and 8:00 a.m. L. reuteri supplementation increased the colonic concentration of lactate, propionate, and butyrate and the expression of occludin, a tight junction protein.[3] These results demonstrate the potent ability of probiotics to alleviate some of the harmful 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 minimizes 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 aligns 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 directly sample the gut, such as the biopsies used in the study, not just blood samples. Unfortunately, biopsies and other direct sampling can often be too invasive and expensive in human trials. This dilemma is essential to consider when extrapolating data collected in scientific studies to make recommendations for probiotic use by individuals.
Cholesterol is a lipid molecule used to build and repair cells and serves as a precursor for producing 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. The small intestine reabsorbs bile acids along with dietary cholesterol, fats, and fat-soluble vitamins such as A, D, E, and K. Cholesterol undergoes recycling via this route between the liver and intestines.[23]
Bacteria in the gut microbiota play significant roles in recycling 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 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 by 2.1 times, LDL 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 before feeding them a cholesterol-raising diet. They gave mice a standard chow diet and assigned them to one of three treatment groups. Group one drank water supplemented with 10,000 CFU of L. reuteri strain CRL 1098 for seven days, group two drank water supplemented with non-fat milk for seven days, and group three drank ordinary 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 seven more 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. 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 human studies 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 serum vitamin D levels 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 significantly reduced insulin resistance, fatty liver, and increased inflammation in rats challenged with a high fructose diet." Click To Tweet
Previous research in animals and humans has demonstrated probiotics' efficacy in improving type 2 diabetes symptoms. This beneficial effect is likely due to probiotics' ability to strengthen the gut barrier and attenuate leaky gut. This strengthened gut barrier reduces whole-body inflammation, improving insulin function and 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]
After 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 people (who are vulnerable to pathogen overgrowth). Live supplements are also more difficult to standardize and store, making heat-killed supplements attractive 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 receiving insulin therapy reported conflicting results. The researchers gave participants either a low dose (100 million CFU) or a 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 a probiotic.[34] A lack of harmonization of research methods (e.g., dose, duration, strain) across trials likely contributes to the inconsistencies 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.
Breast milk is not only a source of nutrition for infants but also an important source of bioactive factors that support the development of a healthy microbiome. Bacteria transfer from the mother's skin to the infant during feeding and accumulate 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 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.[35] This suggests that diet may directly modulate the composition of microbes that colonize the milk ducts and, ultimately, the infant digestive tract.
"L. reuteri supplementation reduced the risk of severe necrotizing enterocolitis by 42 percent and death by 65 percent in preterm infants." Click To Tweet
Breast milk-derived probiotics offer substantial developmental benefits. Preterm neonates (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, 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. Probiotics may be one such treatment with their ability to strengthen the gut barrier, compete with pathogens, and strengthen the host's immune response.[37]
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.[38] 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 to colonize 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.[39]
To determine the effects of probiotic supplementation in preventing 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 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 the age of 12 months.
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, reducing 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 might be due to lower colonization rates of L. rhamnosus compared to L. reuteri, especially in 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.[40]
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 five drops of a probiotic liquid containing 100 million CFU of L. reuteri DSM 17938 or a placebo daily during 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 resulted from too few participants or insufficient probiotic dose for proper gut colonization.[41]
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 decreased by 69 percent, and the risk of death decreased 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 can reduce the risk of necrotizing enterocolitis and late-onset sepsis while improving eating and nutrition in preterm infants. However, more extensive randomized clinical trials are needed to confirm these findings.
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 preventing severe necrotizing enterocolitis and sepsis in preterm infants. The authors included 24 trials in their analysis. They 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. These results strongly support a change in the clinical care of preterm infants.[10]
"Disturbances in the intestinal microbiota that cause gut motor dysfunction and excess gas production may contribute to colicky behavior in infants." Click To Tweet
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.[42] 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.[43]
To determine the effects of L. reuteri supplementation on colic symptoms, 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 colic symptoms and was well-tolerated with no adverse effects.[42]
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 for breastfed infants with colic, but the evidence is inconclusive for formula-fed infants.
Infections causing diarrhea, including rotavirus, are among the most common ailments affecting children worldwide,[44] prompting many to investigate probiotics' benefits. In one study, researchers administered L. 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.[45]
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.[46]
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 preventing childhood diarrhea.[44]
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 diarrhea and respiratory illness cases after three months of supplementation. This effect persisted for a further three months following the end of supplementation, establishing a long-lasting effect on the body. The authors also reported a significant reduction in doctor visits, antibiotic use, absenteeism from school, and parental absenteeism from work.[47]
A later review of eight randomized controlled trials confirmed that L. reuteri supplementation reduces diarrhea duration and prevents community-acquired diarrheal illness.[48]
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 fundamental 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 can tailor treatments to individuals. These cocktails of probiotics and prebiotics may 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.
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 relatively new, there are no established clinical dosage recommendations for L. reuteri or most other probiotics. Please see this page's summary chart of dosages and effects (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 have purchased the supplement. Because probiotic supplements are unregulated in the United States, it is often impossible to ensure their quality. There is also a need for more research investigating the stability of probiotics at room temperature. One study found that Lactobacillus and Bifidobacterium species used as probiotics maintain their viability at room temperature if adequately dehydrated during processing.[49]
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