Bile acids and bile acid modification in health and disease: from novel modifications to therapeutic interventions

Bile acids (BAs) serve dual roles as lipid-digesting molecules and key signaling mediators in metabolism and immune regulation. This review systematically examines: 1.the molecular mechanisms underlying BA-mediated regulation of glucolipid m5etabolism and energy expenditure; 2.host- and microbiota-driven BA modifications (e.g., 3-acylation); 3. therapeutic targeting of BA signaling pathways (FXR/TGR5). We highlight emerging strategies, including novel BA modifications, microbiota interventions, and BA-targeted therapies, which reshape BA homeostasis and show therapeutic potential for metabolic, digestive, hepatobiliary, and neoplastic diseases. Furthermore, we emphasize the central role of BA modifications in metabolic regulation and their pathological implications. Advances in multi-omics and AI-driven approaches deepen mechanistic insights and accelerate the translation of BA-based interventions into clinical practice. Most of the findings discussed in this review are derived from preclinical studies (in vitro and animal models); clinical translation of bile.