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Probiotic Effective for Functional Dyspepsia In Randomized Trial

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Supporting the hypothesis that functional dyspepsia may be caused by dysbiosis in the small bowel, a spore-forming probiotic controlled symptoms in a randomized trial.

The probiotic was effective for multiple symptoms and was associated with a reduction in markers of inflammation and an increase in a putatively healthier fecal bacterial population, according to Lucas Wauters, MD, Ph.D., of the Department of Gastroenterology and Hepatology at University Hospitals, in Leuven, Belgium.

When volunteers who received a placebo were switched to the probiotic for an open-label extension phase of the trial, they quickly achieved the same reduction in symptoms, Dr. Wauters reported at the 2021 Digestive Disease Week (abstract 464).

The 55 evaluable patients with functional dyspepsia were randomly assigned to receive oral probiotics or placebo, both of which were taken twice daily. In the experimental arm, the spore-forming probiotics were Bacillus coagulans MY01 and Bacillus subtilis MY02.

The primary outcome of the trial was a greater than 0.7-point improvement in the 4-point Leuven postprandial distress score (PDS) after eight weeks. Other outcomes, such as epigastric pain and bloating, were recorded in patient diaries.

Patients taking a proton pump inhibitor on enrollment into the study were allowed to continue on the medication. In these patients, a 14C-glycocolic bile acid breath test was administered at both baseline and the end of the trial to detect change in small intestine bacterial overgrowth.

The primary outcome was achieved by 48% of the 25 patients who completed the study on spore-forming probiotics versus 20% of the 30 patients (P=0.03) who completed the study on placebo. Patients who took the probiotics had significantly greater improvement on several specific symptoms, including postprandial fullness (P=0.03) and pain (P=0.02).

The relative effect of the spore-forming probiotics was evaluated in the context of PPIs, which were taken by more than half of the patients. More patients achieved the primary outcome with spore-producing probiotics than placebo, regardless of whether they were a PPI. The advantage of probiotics showed a favorable trend (P=0.1) in patients taking the antireflux medication; although not significant in those not taking PPIs, the number of patients in this subgroup was small, the researchers said.

In the open-label extension phase, which began after the eight-week blinded trial, symptoms improved in patients on placebo who switched to the probiotics, while those initially taking probiotics continued to experience symptom control over the extended follow-up on active therapy, Dr. Wauters reported.

In patients taking PPIs who received the spore-forming probiotics, the proportion with a positive bile acid breath test was significantly reduced (P=0.04) relative to those assigned to placebo, “supporting a reduction in small bowel overgrowth,” Dr. Wauters said.

Both strains of spore-forming probiotic used in the study have been associated with a reduction in mucosal permeability and tissue inflammation in vitro, according to Dr. Wauters. In the new trial, a reduction in inflammation on several measures, including a decrease in the levels of the pro-inflammatory cytokine interleukin (IL)-17 and in Th17 signaling, were observed.

“The reduction in PDS scores was only seen in those who also had a reduction in IL-17 or Th17-positive cells,” said Dr. Wauters, who added that the probiotic strains were well tolerated.

A Shift in Focus

In the effort to understand and treat functional dyspepsia, “research has shifted increasingly from the stomach to the proximal small bowel or duodenum,” Dr. Wauters said. The increase in Faecalibacterium prausnitzii on probiotic treatment that he and his colleagues observed in the new study is consistent with a favorable effect on the microbiome in this area of the gut, he noted.

Conversely, PPIs, which are frequently offered to patients with functional dyspepsia, might ultimately disturb the microbiome in the proximal small bowel, contributing to symptoms of dyspepsia even if they initially provide some relief, he said.

In the context of other evidence that the duodenal microbiome is altered in patients with functional dyspepsia, this has emerged as an attractive therapeutic target, according to Nicholas J. Talley, MD, PhD, a distinguished laureate professor at the University of Newcastle, in Australia.

“Wauters et al present important new data that a mixed probiotic can improve functional dyspepsia symptoms in about half of the patients,” Dr. Talley said. However, he was not certain they had the correct mechanism.

“While the authors speculate this [effect] is via improving small intestinal bacterial overgrowth based on breath testing, it would seem more plausible this is related directly to altering the duodenal microbiome,” Dr. Talley told Gastroenterology & Endoscopy News. He indicated that the answers to additional questions have the potential to move the field forward.

“Why only 50% response and what exactly predicts response is unknown, and whether the natural history of functional dyspepsia is altered by this probiotic is also unknown,” he said. Despite this, Dr. Talley considered the substantial rate of response to be a proof of concept.

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Schedule10 Jun 2023