Objective: Six weeks of treatment with liraglutide or colesevelam improves the symptoms of bile acid diarrhea (BAD). Colesevelam binds excess amounts of diarrhea-causing bile acids in the colon whereas the mechanism of action for liraglutide remains elusive; however, it may involve decreased small intestinal motility, leading to an increased passive bile acid absorption in the small intestine. Here, we examined the impact of colesevelam and liraglutide on both the concentrations of bile acids present in serum and feces to better understand the two drugs’ mode of actions.
Methods: The five most abundant bile acid species were analyzed in serum and fecal samples from a randomized, double-blind, controlled trial at baseline and after three and six weeks of orally administered colesevelam (1,875 mg twice daily, n = 26) or subcutaneously administered liraglutide (uptitrated by weekly increments of 0.6 mg from 0.6 to 1.8 mg daily, n = 26) in patients with ⁷⁵selenium-homotaurocholic acid test-verified, idiopathic, or post-cholecystectomy BAD. Fecal microbiota composition was analyzed by 16S rRNA gene amplicon sequencing at the same time points.
Results: Colesevelam increased the fecal concentrations of all bile acid species. Concomitantly, serum concentrations of secondary bile acids decreased. Liraglutide induced a small, but statistically significant increase in serum unconjugated bile acid concentrations without affecting fecal bile acid concentrations. Microbial analyses revealed no significant changes in gut microbiome composition as determined alpha- or beta-diversity metrics with either treatment.
Conclusion: Colesevelam and liraglutide exhibit distinct effects on serum and fecal bile acid concentrations. Colesevelam reduces the serum levels of secondary bile acids and promotes fecal excretion. On the other hand, liraglutide enhances the serum levels of unconjugated bile acids, potentially through its ability to slow down small intestinal transit time allowing more time for bile acid–bacteria interactions and passive absorption.

Martin Kårhus

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