Secondary bile acid metabolism

Secondary bile acid metabolism is a multi-step biochemical process wherein primary bile acids synthesized in the liver, such as cholic acid and chenodeoxycholic acid, are chemically modified by the gut microbiota into secondary bile acids, most notably deoxycholic acid (DCA) and lithocholic acid (LCA) (Source: NIH, PubMed). This transformation involves microbial enzymes such as bile salt hydrolases (BSH) and 7α-dehydroxylases, which remove glycine or taurine conjugates and hydroxyl groups, respectively (Source: Nature Reviews Gastroenterology & Hepatology). These secondary bile acids serve as potent signaling molecules that bind to and modulate the activity of the Farnesoid X receptor (FXR) and the G protein-coupled bile acid receptor 1 (GPBAR1/TGR5), thereby regulating glucose, lipid, and energy metabolism (Source: PubChem). Dysregulation of secondary bile acid metabolism is strongly linked to various pathologies, including cholestatic liver diseases, metabolic syndrome, and an increased risk of colorectal cancer due to the cytotoxic and pro-inflammatory properties of certain secondary metabolites (Source: Wikipedia, Journal of Clinical Investigation). Therapeutic intervention typically involves the use of synthetic bile acid analogs like obeticholic acid to activate feedback inhibition, or bile acid sequestrants and transport inhibitors to reduce the total bile acid pool (Source: StatPearls). Understanding this pathway is critical for developing microbiome-targeted therapies and treatments for metabolic and hepatobiliary disorders.

Other names

Bacterial bile acid transformationMicrobial bile acid metabolismSecondary bile acid synthesis pathway

Modulation of bile acid pools via Farnesoid X receptor (FXR) agonism, Takeda G protein-coupled receptor 5 (TGR5) activation, inhibition of apical sodium-dependent bile acid transporter (ASBT/IBAT), or sequestration of bile acids in the gut to alter feedback loops.