Bile acid metabolism pathway

Bile acid metabolism pathway" refers to the complex network of enzymatic and microbial processes mediating the synthesis, transformation, transport, and recycling of bile acids. This pathway encompasses liver synthesis of primary bile acids via enzymes such as cholesterol 7α-hydroxylase (CYP7A1) and sterol-27-hydroxylase (CYP27A1), their conjugation and secretion, transformation by gut microbiota into secondary bile acids (notably through the 7α-dehydroxylation route), and hepatic reuptake through the enterohepatic circulation. The pathway also includes interaction with multiple receptors, such as the farnesoid X receptor (FXR), Takeda G protein-coupled receptor 5 (TGR5 or GPBAR1), and others (VDR, PXR, CAR, S1PR2). Bile acid metabolism is tightly regulated by feedback mechanisms involving FXR and FGF19/15 signaling to prevent toxic bile acid accumulation and maintain metabolic homeostasis[1][3][5][4]. Disruption of this pathway is implicated in a range of metabolic, hepatic, and inflammatory diseases, and several drugs target distinct enzymes or receptors within these pathways. Note: "Bile acid metabolism pathway" is not a single molecular target (receptor, enzyme, or transporter), but a system-level collection of processes and regulatory molecules. Therefore, it is not considered a therapeutic target per se but rather describes a set of pathways and potential points of intervention[2][4]. For drug development and mechanistic insight, the focus should be on individual enzymes (e.g., CYP7A1), receptors (e.g., FXR, TGR5), or microbial enzymes mediating specific steps within bile acid metabolism.

Other names

Bile acid metabolic pathwayBile acid metabolismBA metabolic pathway

Modulation of bile acid synthesis and reabsorption FXR receptor agonism/antagonism Alteration of gut microbial pathways (e.g., 7α-dehydroxylation)[2][5]