Tae Hyung Won, Frank C Schroeder
Covering: 2019 to April 2026Bile acids, originally identified as digestive emulsifiers, are now recognized as signaling molecules at the nexus of metabolism and immunity. Recent advances in metabolomics have revealed unexpected chemical diversity of BAs, derived from previously unrecognized conjugation pathways involving both the gut microbiota and the host. This includes microbial conjugation of the bile acid carboxy terminus with diverse amino acids and other biogenic amines as well as host-derived conjugation with cysteamine derivatives. In addition, microbial acylation of the steroid core has been shown to introduce succinyl, acetyl, and other chemical modifications, including expansion of the canonical bile acid carbon skeleton. This review synthesizes recent discoveries (2019-2026) in bile acid conjugation chemistry and highlights how the expanded bile acid diversity regulates host physiology through activation of different nuclear receptors and G-protein coupled receptors, including therapeutic implications for metabolic and immune disorders such as non-alcoholic steatohepatitis, inflammatory bowel disease, and cardiometabolic diseases. The emerging picture reveals that bile acid pools result from an intricate network of host-microbe metabolic pathways, and that considering both host and microbial contributions is essential for understanding bile acid biology in health and disease.