Mechanisms of key gut microbial metabolites: SCFAs, BAs, and TDMs.

Gut microbial metabolites, particularly short-chain fatty acids (SCFAs), bile acid (BAs) derivatives, and tryptophan-derived metabolites (TDMs), act as signaling molecules, receptor ligands, and epigenetic modulators in regulating host metabolic and immune homeostasis. They exert local effects in the gut and reach distant tissues via hepatic, lymphatic, neural, and immune-hormonal routes, thereby regulating immunity, metabolism, and neural function. Disruptions in these pathways are associated with inflammatory diseases, neurodegeneration, and cancer. This review discusses the importance of SCFAs, BAs, and TDMs in different host metabolic and immunological contexts, dissects their molecular mechanisms of action on target cells, evaluates the therapeutic implications of targeting these microbial pathways, and outlines a roadmap for possible future clinical translations.