Gut microbiota–bile acid metabolism axis (GM-BA axis)

The gut microbiota–bile acid metabolism axis is a complex bidirectional communication system that integrates host metabolism with microbial activity. Bile acids are synthesized from cholesterol in the liver and secreted into the duodenum, where they facilitate lipid absorption; subsequently, gut bacteria chemically modify these primary bile acids into secondary bile acids through deconjugation and dehydroxylation (PubMed: 28232163). These bile acid species serve as potent signaling molecules that activate specific host receptors, most notably the Farnesoid X Receptor (FXR) and the Takeda G protein-coupled receptor 5 (TGR5), which regulate systemic glucose, lipid, and energy metabolism (PMC6835810). Dysregulation of this axis, often characterized by microbial dysbiosis and altered bile acid pools, is a central driver in the pathogenesis of metabolic and cholestatic liver diseases. Therapeutic interventions aim to restore balance by modulating receptor activity or altering the bile acid pool through pharmacological inhibitors, sequestrants, or microbiome-based therapies (PubMed: 33154518).

Other names

Gut-liver-bile acid axisBile acid-microbiota crosstalkEnterohepatic circulation-microbiome axisMicrobiota-bile acid signaling pathway

Drugs targeting this axis typically act as agonists for nuclear receptors like the Farnesoid X Receptor (FXR) to inhibit bile acid synthesis, or as inhibitors of the Apical Sodium-dependent Bile acid Transporter (ASBT) to reduce bile acid reabsorption. Others act as bile acid sequestrants to lower systemic levels or as G protein-coupled receptor (TGR5) agonists to improve metabolic signaling (PubMed: 33154518; PMC6835810).