The role of bile acids in functional GI disorders.

Background: Bile acids are increasingly implicated in the pathogenesis of functional GI disorders. New mechanisms have recently been described in the irritable bowel syndrome, chronic diarrhea and chronic idiopathic constipation. Identification of bile acid signaling through farnesoid X receptor (FXR), transmembrane G-coupled receptor 5 (TGR5) and fibroblast growth factor 19 (FGF19) has led to the development of new, directly acting therapeutic agents. Despite these advances primary bile acid diarrhea remains under-recognized partly because of the lack of a widely available diagnostic test.

Purpose: In this review we will summarize the effects of bile acids on bowel function throughout the gastrointestinal tract and their roles in the pathogenesis of functional diseases. We will review established diagnostic tests and therapies for functional heartburn, dyspepsia and bile acid diarrhea. There will be a particular emphasis on recent trial data for emerging therapies such as Elobixibat and Obeticholic acid and novel diagnostic tests for bile acid diarrhea such as 7α-Hydroxy-4-cholesten-3-one (C4) and FGF19. Finally we will discuss future directions for research in this rapidly evolving field, such as bacterial bile acid modification and identification of genetic anomalies associated with functional disorders.