Microbiome–liver axis via bile salt metabolism

The microbiome–liver axis via bile salt metabolism is a complex physiological system involving the bidirectional communication between the gut microbiota and the liver, primarily mediated by bile acid signaling (Wahlström et al., 2016). Bile acids are synthesized in the liver and undergo extensive modification by gut bacteria, including deconjugation by bile salt hydrolases and 7α-dehydroxylation to form secondary bile acids (Ridlon et al., 2014). These molecules serve as ligands for key receptors such as the Farnesoid X receptor (FXR) and the G protein-coupled bile acid receptor 1 (TGR5), which regulate critical processes including lipid and glucose metabolism, energy expenditure, and inflammatory pathways (Arab et al., 2017). Dysregulation of this axis is a hallmark of several metabolic and cholestatic conditions, such as metabolic dysfunction-associated steatotic liver disease (MASLD) and primary biliary cholangitis (PBC) (Trauner et al., 2017). Therapeutic strategies often focus on modulating specific components of this axis, such as using FXR agonists or bile acid sequestrants, to restore metabolic balance and reduce hepatic inflammation (Adorini et al., 2012).

Other names

Gut-liver axisBile acid-microbiome axisEnterohepatic circulation of bile acidsBile acid-gut microbiota crosstalk

Modulation of the bile acid pool composition and signaling through nuclear receptors (e.g., Farnesoid X receptor) and membrane receptors (e.g., TGR5), or inhibition of bile acid transporters (e.g., ASBT), to regulate metabolic and inflammatory pathways.