Secondary bile acid (SBA)

Secondary bile acids, primarily deoxycholic acid (DCA) and lithocholic acid (LCA), are metabolites produced by the intestinal microbiota through the 7-alpha-dehydroxylation of primary bile acids synthesized by the liver. They function as integral signaling molecules that bridge the gut microbiome and host physiology by activating specific receptors such as the farnesoid X receptor (FXR) and the TGR5 G protein-coupled receptor, which regulate systemic metabolism and energy expenditure. While essential for lipid digestion and metabolic health, an imbalance in the fecal secondary bile acid pool is strongly linked to disease. Elevated levels of DCA and LCA are associated with the promotion of colorectal cancer via DNA damage and oxidative stress, whereas a depletion of these metabolites can facilitate the colonization of pathogens like Clostridioides difficile. In drug development, these molecules are primarily viewed as metabolic markers or ligands whose levels and signaling pathways are modulated by bile acid sequestrants, probiotics, or synthetic receptor agonists to treat cholestatic, metabolic, and inflammatory disorders.

Other names

7-alpha-dehydroxylated bile acidMicrobiota-derived bile acidDeoxycholic acidLithocholic acidDCALCABacterial bile acid metabolites

Bile acid sequestrants (e.g., cholestyramine) bind to secondary bile acids in the gastrointestinal tract to prevent their reabsorption and promote excretion. Antibiotics and probiotics modulate the gut microbiota composition to alter the enzymatic conversion (7-alpha-dehydroxylation) of primary bile acids into secondary bile acids. Synthetic agonists like obeticholic acid mimic bile acid signaling at the FXR receptor to regulate bile acid synthesis and transport.