Abstract
Secondary bile acids (SBAs) attracted interest due to their regulatory functions in gut microbial ecology and immune responses. These intricate microbial transformations decisively shape the biochemical properties of SBAs. Recent advancements in artificial intelligence and mass spectrometry technologies have substantially expanded our understanding of the diversity within the SBAs pool. To date, hundreds of SBAs, a minor portion of the natural SBA repertoire, have been identified, alongside the prediction of tens of thousands of associated enzymes. Integrative multi-omics studies have further substantiated the role of SBAs in the pathogenesis of autoimmune diseases. This review synthesizes current knowledge on the microbial modification of bile acids, their effects on gut microbial ecology and immune function, with a particular emphasis on autoimmune disorders. Collectively, these findings highlight SBAs as critical regulators of gut microbiota and immune system homeostasis, with their functions intricately linked to their molecular structures.