Probiotics No Better Than Placebo for Gastroenteritis

Children with gastroenteritis who receive probiotics have no better clinical outcomes than those who receive placebo, according to two studies published online November 21 in the New England Journal of Medicine.

"In children who presented to the emergency department with gastroenteritis, twice-daily administration of a combined Lactobacillus rhamnosus–L. helveticus probiotic did not prevent the development of moderate-to-severe gastroenteritis within 14 days after enrollment," write Stephen B. Freedman, MDCM, from Alberta Children's Hospital, Calgary, Canada, and colleagues.

Acute gastroenteritis is a significant cause of morbidity and mortality in children worldwide and accounts for about 1.7 million visits to US emergency departments (EDs) each year.

However, although probiotic use is on the rise in the United States, including among persons with intestinal infections, data to support using them for this indication are limited, David Schnadower, MD, MPH, from Cincinnati Children's Hospital Medical Center, Ohio, and colleagues stress in the second study.

With this in mind, the research groups conducted separate randomized double-blind trials to investigate the effectiveness of using probiotics to manage acute gastroenteritis in children.

The two prospective studies included a total of 1770 children aged 3 to 48 months who presented to pediatric EDs with moderate-to-severe, acute infectious gastroenteritis.

In both trials, in addition to receiving standard therapy for gastroenteritis during their ED visit, children were also randomly assigned to receive a 5-day course of twice-daily probiotics or placebo.

The probiotics comprised formulations that are readily available for purchase over the counter in Canada and the United States. Freedman and colleagues used a preparation of L. rhamnosus that also contained a small amount of the probiotic strain L. helveticus. Schnadower and colleagues used a product containing only L. rhamnosus GG.

In both trials, probiotics failed to perform better than placebo at reducing the progression or severity of gastroenteritis.

Combination Probiotic Not Better Than Placebo

In the study by Freedman and colleagues, moderate-to-severe gastroenteritis occurred within 14 days after enrollment in 108 of 414 children (26.1%) receiving probiotics and in 102 of 413 children (24.7%) receiving placebo (odds ratio [OR], 1.06; 95% CI, 0.77 - 1.46; P = .72).

Similarly, there were no significant differences between the two groups in the median duration of diarrhea (52.5 and 55.5 hours; P = .31) or vomiting (17.7 and 18.7 hours; P = .18).

Adverse event (AE) rates were similar between the probiotic and placebo groups (34.8% and 38.7%; OR, 0.83; 95% CI, 0.62 - 1.11; P = .21). However, two children who received placebo had serious AEs. One had a febrile seizure, and one received a diagnosis of Kawasaki disease.

Single Probiotic Not Superior to Placebo

In the study by Schnadower and colleagues, the gastroenteritis clinical severity score was 9 or greater in 55 of 468 children (11.8%) receiving probiotics and in 60 of 475 (12.6%) receiving placebo. The relative risk of a moderate-to-severe episode of acute gastroenteritis with probiotic was 0.96 (95% CI, 0.68 - 1.35; P = .83).

There were no significant differences between the two groups in the median duration of diarrhea (49.7 and 50.9 hours; P = .26) or vomiting (0 hours in both groups; P = .17).

Wheezing was reported in five children in the probiotic group and in no children in the placebo group (P = .03).

Other Probiotics Might Be Helpful, Editorialist Says

In an accompanying editorial, J. Thomas LaMont, MD, from Beth Israel Deaconess Medical Center, Boston, Massachusetts, explains that although some professional societies recommend using probiotics to treat acute gastroenteritis, data to support this are mostly "based on studies that have been underpowered or had methodologic problems related to the trial design and choice of appropriate endpoints."

In contrast, he highlights that these two trials were similarly well-designed with similar primary endpoints and produced high-quality combined data on a large number of participants.

"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," he writes.

However, it remains possible that other probiotics could potentially be useful for treating acute gastroenteritis in children, he adds, because of the many probiotics with different properties that are available.

"With their low cost and minimal toxic effects, probiotics have potential for the treatment of a variety of gastrointestinal and other diseases, but rigorous trials such as those described in this issue of the Journal are required to determine any potential efficacy or effectiveness," he concludes.

The study by Freedman and colleagues was supported by the Canadian Institutes of Health Research; Alberta Children's Hospital Foundation; Calgary Laboratory Services; Provincial Laboratory for Public Health–Alberta Public Laboratories; Luminex; and Copan Italia. The study by Schadnower and colleagues was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development; Emergency Medical Services for Children Program of the Maternal and Child Health Bureau, Health Resources, and Services Administration; Washington University Biobank Core, supported by the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health; and iHealth. Freedman has reported receiving study drug (probiotic) and placebo from Lallemand Health Solutions for another study. Sherman has reported serving as the scientific director of the Canadian Institutes of Health Research, Institute of Nutrition, Metabolism and Diabetes. Disclosures for the other authors are listed in the articles. The editorialist has reported no relevant financial relationships.

N Engl J Med. Published online November 21, 2018. Study 1, Study 2, Editorial

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