A Microbiome Bust? Lack of Probiotic Benefit for Acute Pediatric Gastroenteritis

William F. Balistreri, MD


January 31, 2019

In This Article

New Insight Into Their Efficacy

Two randomized, double-blind, placebo-controlled trials document the inability of probiotics to alter the course of acute gastroenteritis in young children.[22,23] In designing these related studies, the authors noted the aforementioned methodologic limitations in the clinical trials that prompted recommendations for the use of probiotics: small sample sizes, a lack of quality control of the probiotics, outcomes of questionable relevance, attrition biases, unclear randomization strategies, and inadequate concealment of treatment assignments.[1,9,20,21] In addition, they stated that while numerous individual symptoms have been used as outcomes, evaluations that incorporate the duration and the frequency of both diarrhea and vomiting are lacking.[1,3,22,23,24,25]

The studies compared the effectiveness of placebo against different strains of the probiotic Lactobacillus in 1857 infants and children with acute infectious gastroenteritis in Canada and the United States.[22,23] These probiotic formulations are available over the counter in both countries.

Freedman and colleagues[22] conducted a randomized, double-blind trial involving 886 children aged 3-48 months with gastroenteritis who presented to six pediatric emergency departments in Canada. These children received either a 5-day course of placebo or a combination probiotic product containing Lactobacillus rhamnosus R0011 and L helveticus R0052, at a dose of 4.0×109 colony-forming units twice daily. The primary outcome was moderate to severe gastroenteritis, defined as an illness episode with a total score of ≥ 9 on the modified Vesikari scale, which incorporates assessment of diarrhea, vomiting, and fever. Moderate to severe gastroenteritis within 14 days after enrollment occurred in 26% of the children assigned to receive the probiotics and in 25% assigned to receive the placebo (odds ratio, 1.06).

Schnadower and colleagues[23] conducted a parallel prospective, randomized, double-blind trial in children younger than 4 years with acute gastroenteritis who presented to one of 10 geographically diverse pediatric emergency departments in the United States. Participants also received a 5-day course of L rhamnosus GG (minus the L helveticus) at a dose of 1×1010 colony-forming units twice daily or a matching placebo. Those subjects who received L rhamnosus GG did not have better outcomes than those who received placebo. The modified Vesikari scale score for the 14-day period after enrollment was ≥ 9 in 12% of the children assigned to receive L rhamnosus GG and in 13% who received placebo (relative risk, 0.96).

In both studies, there were no significant differences between the probiotic recipients and the placebo recipients in the mean duration of diarrhea or vomiting, the percentages of participants with unscheduled visits to a healthcare provider or day-care absenteeism, or the rate of household transmission. Of note, < 50% of the stool samples were positive for viral pathogens, and no pathogen was detected in 43%. This study reflects a smaller number of children with rotavirus infection than in earlier studies.[22] In both trials, the rates of adverse events were similar in the group who received probiotics and the group who received placebo. Taken together, neither of these large, well-done trials provides support for the use of probiotics containing L rhamnosus to treat moderate to severe gastroenteritis in children.

The authors did note several limitations in their studies. They relied on parental reports of adherence and symptoms, raising the possibility of inaccurate recall bias, as well as the potential for inconsistent and selective reporting and post-hoc modifications with the use of composite outcome measures. In addition, the trial medication required refrigeration over the 5 days, thus it could have been exposed to temperature extremes in the home or during transport, which could have affected bacterial viability.

In comparison to previous studies that reported a benefit of probiotics in acute gastroenteritis, potential explanations for the negative effect include the use of a validated composite outcome measure that incorporates multiple aspects of the severity of the gastroenteritis, rather than basis on individual symptoms, as in other studies.[24,25] These findings should be considered in the context of the clinical trials that have demonstrated positive outcomes. The results with the specific probiotic used may not be generalizable to other products on the market, and benefit may occur in other populations or for different indications.[1,22,23]

In an accompanying editorial, LaMont[3] pointed out that given the large number of probiotic agents now available and their various mechanisms of action, abilities to colonize the bowel, and the narrow potential efficacy for specific diseases, the possibility remains that probiotics other than L rhamnosus might be effective in children with infectious diarrhea. Thus, it is cautioned that these results should not elicit the generalization that probiotics do not work.

Bottom Line

As noted, the rigor of the research design of these two related pragmatic studies raises the question of the recommendations to use L rhamnosus GG in the treatment of children with acute gastroenteritis.[1,22,23] These negative clinical trials will inform clinicians and guideline committees regarding the use of either of these specific probiotic formulations in children with diarrhea. Given the limitations of meta-analyses, rigorous trials are required to determine the efficacy or effectiveness in a variety of gastrointestinal and other diseases.[1]

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