Bile acid metabolism (microbial)

Primary bile acids — cholic acid and chenodeoxycholic acid — are synthesised in the liver from cholesterol and conjugated to glycine or taurine before secretion into the small intestine. Gut bacteria transform them via deconjugation, 7α-dehydroxylation, epimerisation and oxidoreduction into a structurally diverse pool of secondary and tertiary bile acids, including deoxycholic acid (DCA), lithocholic acid (LCA), ursodeoxycholic acid (UDCA) and isoallo-lithocholic acid (isoallo-LCA). These secondary bile acids function as signalling molecules beyond their classical roles in dietary fat emulsification: they activate the nuclear receptor FXR and G-protein-coupled receptor TGR5, modulating glucose homeostasis, lipid metabolism, energy expenditure and innate immune tone. Isoallo-LCA is of particular interest in longevity research because it potently induces the differentiation of immunosuppressive RORγt⁺ regulatory T cells and is enriched in supercentenarians. The composition of the secondary bile acid pool is critically dependent on microbiota composition — notably species in Lachnospiraceae and Ruminococcaceae — and is substantially altered in ageing, obesity and inflammatory bowel disease.