Bile acids as mediators of microbiota signaling in entero-hepatic disorders

This review examines the structure and the functional role of the signaling network formed by bile acids as their receptors in mediating chemical communication between the intestinal microbiota and host in entero-hepatic disorders, such as inflammatory bowel disease (IBD) and Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD). In the last decade, advances in analytical technologies and bioinformatic approaches, including metabolomics and reverse metabolomics, have greatly expanded our understanding of bile acid metabolism. These studies have shown that the intestinal microbiota transforms primary bile acids synthesized in the liver from cholesterol into a highly diverse family of bioactive mediators. Hundred of "classical" secondary bile acids and Microbial Derived Bile Acids (MDBA) have been identified and characterized for their role in regulating the activity of widely expressed receptors, including the Farnesoid-x-receptor (FXR), the G protein-coupled bile acid receptor (GPBAR1) and the retinoid-related orphan receptor (RORγ). Simultaneous characterization of microbial species expressing bile acid-related genes is emerging as a valuable tool for disease phenotyping. One example is bile salt hydrolase (BSH), an enzyme that catalyzes bile acid deconjugation. In parallel, profiling bile acid composition in biological compartments such as feces and blood may help identify associations between microbiota dysbiosis and diseases including IBD and metabolic dysfunction-associated steatohepatitis (MASH). The review also examines therapeutic approaches that could be developed to exploit this novel conceptual framework.