Probiotics Show Promise for Symptoms of Functional GI Disorders

Spore-forming probiotics were safe and effective for treating functional dyspepsia symptoms in a small randomized Belgium trial.

In an intention-to-treat analysis involving 55 patients with functional dyspepsia, a greater proportion of those given probiotics achieved clinical response at 8 weeks compared to patients given placebo (48% vs 20%, respectively; RR 1.95, 95% CI 1.07-4.11, P=0.028), reported Tim Vanuytsel, MD, PhD, from University Hospitals Leuven in Belgium, and colleagues.

Probiotics were also well-tolerated, with a similar proportion of probiotics and placebo groups reporting adverse events, such as gastritis, flu-like symptoms, or skin infections, and no serious treatment-related adverse events, the authors wrote in The Lancet Gastroenterology and Hepatology.

Clinical responses appeared to favor the probiotic group regardless of proton-pump inhibitor (PPI) use:

• With PPI: 46% vs 13%; RR 2.60 (95% CI 0.98-9.36)
• Without PPI: 50% vs 27%; RR 1.62 (95% CI 0.78-4.05)

“Since probiotics are safe and well-tolerated, these new generation, spore-forming probiotics can be used early on in the treatment of functional dyspepsia,” Vanuytsel told MedPage Today. “Unfortunately, the therapy is not available yet in the American market.”

Prior functional dyspepsia treatments have not shown sufficient efficacy or safety. Long-term PPI use can alter intestinal microbiota (causing dysbiosis) and increase the risk for Clostridium difficile infections, Vanuytsel and colleagues noted. One prior trial suggested probiotics in yogurt (Lactobacillus gasseri) could help treat dyspepsia.

Authors reported that their study is the first to evaluate spore-forming probiotics. Since endospores can survive harsh environments, such as the presence of hydrochloric acid in the stomach, they also have prolonged intestinal survival, which could make them more effective, the authors said.

They attempted to evaluate the safety and efficacy of these probiotics, either administered as a monotherapy or added with PPIs for long-term functional dyspepsia treatment.

From June 2019 to March 2020, the group randomized 68 adults with functional dyspepsia from a single center to receive 2 months of probiotic capsules containing the bacteria Bacillus subtilis (MY02) and Bacillus coagulans (MY01) or twice-daily placebo. Probiotic capsules contained 50 mg of 2.5 × 10⁹ colony forming units (CFUs) of endospores mixed with maltodextrin, a food additive.

Monthly patient PAGI-SYM (patient assessment of upper gastrointestinal symptom severity index) questionnaires assessed symptom severity and quality of life. The primary endpoint was a minimum reduction of 0.7 on the Leuven Postprandial Distress Scale among patients with a baseline post-prandial distress syndrome (PDS) score of at least 1.

Mean age of participants was 40, about 75% were women, over 89% were white, and about half were on PPIs (a stratification factor). More than 60% of patients presented with PDS. For the intention-to-treat response analysis, seven patients from the probiotics arm were excluded due to a baseline PDS score <1, as were six assigned to placebo.

Compared to PDS scores at baseline, the decline at 8 weeks was significantly higher among those taking probiotics compared to placebo, though the difference in epigastric pain syndrome scores “was significant with probiotics, but not placebo,” the authors noted. PAGI-SYM scores were similar after 8 weeks in both groups.

Probiotics did increase stool bacteria, Faecalibacterium and Roseburia.

“We not only found a clinical benefit, but we were also able to get some insight into the mechanism,” Vanuytsel said. “After 16 weeks of treatment, we saw a decrease in IL-17 and Th17 [T-helper] cells, which are inflammatory markers, and an increase of bacteria in the stools of which we know that they can have beneficial effects on gut health.”

Both probiotics and placebo groups reported adverse events (16% vs 33%, respectively). Two serious adverse events, syncope and appendicitis, were also reported, but were unrelated to the study medication, according to the authors. There were no treatment-related deaths.

However, Grace Burns, PhD, from the University of Newcastle in Australia, and colleagues pointed out several limitations to the findings in an accompanying editorial.

“Not all individuals are receptive to probiotics and responses are [individualized]: some individuals are probiotic-permissive and some are probiotic-resistant,” they wrote. “As such, it remains unclear as to whether the heterogeneity in functional dyspepsia presentation might mean that some patient subgroups respond better than others to probiotics.”

Study limitations noted by the study authors included its limited duration and generalizability. Patients were also not selected based on PDS severity.

“It remains to be seen if spore-forming probiotic cocktails have long-term efficacy in symptom management for functional dyspepsia, and further characterisation of the immune and microbial profiles at the gastroduodenal level is required to establish localized response,” the editorialists said.