TOPLINE

A high-dose eight-strain probiotic formulation taken for 3 weeks was well tolerated and resulted in a reduction in the percentage of fecal primary bile acids, particularly chenodeoxycholic acid, along with changes in gut microbiome composition, among patients with bile acid malabsorption.

METHODOLOGY

• Bile acid malabsorption is linked to increased permeability in the intestines and colon, faster colonic transit, and changes in the stool microbiome. The microbiota are known to help regulate bile acid levels; therefore, microbiome-based interventions such as the use of probiotics may influence bile acid metabolism.
• Researchers conducted a randomized placebo-controlled trial at Mayo Clinic to evaluate the effects of an eight-strain probiotic in 24 patients with chronic diarrhea due to bile acid malabsorption.
• Adult participants with biochemically confirmed bile acid malabsorption (serum 7-alpha-hydroxy-4-cholesten-3-one [7-alpha-C4] levels > 52.5 ng/mL, fecal 48-hour total bile acid excretion > 2337 μmol/48 hours, or a primary bile acid percentage > 5% from a 48-hour stool collection or > 10% from a single stool sample) and a 7-day stool consistency average ≥ 5 on the Bristol Stool Form Scale were included.
• Participants were randomly assigned to receive either the De Simone formulation eight-strain probiotic (900 billion colony-forming units via two sachets) or a maltose placebo powder three times daily for 21 days; 22 patients were included in the final analysis.
• The primary endpoint was the change in fecal bile acid levels, particularly the percentage of fecal primary bile acids. Secondary endpoints were changes in total fecal bile acid levels and short-chain fatty acid levels in a single stool sample, fasting serum 7-alpha-C4 levels, intestinal permeability, stool consistency and frequency, the composition and diversity of the fecal microbiome, and the fecal metabolome.

TAKEAWAY

• At baseline, six participants had elevated serum 7-alpha-C4 levels or both elevated serum 7-alpha-C4 and fecal primary bile acid levels. Seven participants had normal serum 7-alpha-C4 levels with elevated primary bile acid levels, and 11 had a normal bile acid profile.
• Probiotic supplementation was associated with a reduction in the percentage of fecal primary bile acids, whereas placebo was associated with an increase (P = .006). This reduction was primarily driven by a lower percentage of chenodeoxycholic acid in stool (P = .0122).
• The fecal microbiome composition differed between the groups after the intervention, with beta-diversity analysis showing separation between the placebo and probiotic groups at the end of treatment (P = .002) but not at baseline (P = .44); this difference was driven by probiotic-specific bacterial species.
• No significant between-group differences were observed for stool frequency, stool consistency, ease of passage, sensation of complete evacuation, serum 7-alpha-C4 levels, fecal short-chain fatty acid concentrations, or intestinal permeability. Both treatments were well tolerated, and the observed adverse events were deemed unrelated or unlikely to be linked to the assigned treatments.

IN PRACTICE

“[The] study demonstrated promising preliminary data in improving biochemical parameters among individuals with BAM [bile acid malabsorption],” the authors of the study wrote. “Future research with a larger sample size and longer duration treatment is required to further appraise the therapeutic effect of this probiotic preparation,” they added.

SOURCE

This study was led by John A. Damianos, Clinical Enteric Neuroscience Translational and Epidemiological Research, Division of Gastroenterology and Hepatology, Mayo Clinic in Rochester, Minnesota. It was published online in Alimentary Pharmacology & Therapeutics.

LIMITATIONS

The sample size was small. The 3-week study duration may have been insufficient to detect effects on other biochemical parameters and symptoms. While all patients had prior biochemically confirmed bile acid malabsorption diagnoses, only 12 of 24 enrolled participants showed continued evidence of altered bile acid metabolism at baseline, introducing the possibility of false negative results.

DISCLOSURES

ExeGi Pharma provided a grant to support this study. One author disclosed receiving clinical trial research funding from ExeGi Pharma as well as consulting fees from ExeGi Pharma and speaker bureau fees from i-Health. Another author reported serving on advisory boards for Pendulum and 32 Biosciences and holding equity options in 32 Biosciences.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.