Bile acid physiology

The primary bile acids (BAs) are synthetized from cholesterol in the liver, conjugated to glycine or taurine to increase their solubility, secreted into bile, concentrated in the gallbladder during fasting, and expelled in the intestine in response to dietary fat. BAs are also bio-transformed in the colon to the secondary BAs by the gut microbiota, reabsorbed in the ileum and colon back to the liver, and minimally lost in the feces. BAs in the intestine not only regulate the digestion and absorption of cholesterol, triglycerides, and fatsoluble vitamins, but also play a key role as signaling molecules in modulating epithelial cell proliferation, gene expression, and lipid and glucose metabolismby activating farnesoid X receptor (FXR) and G-protein-coupled bile acid receptor-1 (GPBAR-1, also known as TGR5) in the liver, intestine, muscle and brown adipose tissue. Recent studies have revealed the metabolic pathways of FXR and GPBAR-1 involved in the biosynthesis and enterohepatic circulation of BAs and their functions as signaling molecules on lipid and glucose metabolism.