Bile acids facilitate intestinal nutrient absorption and biliary
cholesterol secretion to maintain
bile acid homeostasis, which is essential for protecting liver and other tissues and cells from
cholesterol and
bile acid toxicity.
Bile acid metabolism is tightly regulated by
bile acid synthesis in the liver and
bile acid biotransformation in the intestine.
Bile acids are endogenous
ligands that activate a complex network of
nuclear receptor farnesoid X receptor and membrane
G protein-coupled
bile acid receptor-1 to regulate hepatic
lipid and
glucose metabolic homeostasis and energy metabolism. The gut-to-liver axis plays a critical role in the regulation of enterohepatic circulation of
bile acids,
bile acid pool size, and
bile acid composition.
Bile acids control gut bacteria overgrowth, and gut bacteria metabolize
bile acids to regulate host metabolism. Alteration of
bile acid metabolism by high-fat diets, sleep disruption, alcohol, and drugs reshapes gut microbiome and causes
dysbiosis,
obesity, and metabolic disorders. Gender differences in
bile acid metabolism, FXR signaling, and gut microbiota have been linked to higher prevalence of
fatty liver disease and
hepatocellular carcinoma in males. Alteration of
bile acid homeostasis contributes to cholestatic
liver diseases, inflammatory diseases in the digestive system,
obesity, and diabetes.
Bile acid-activated receptors are potential therapeutic targets for developing drugs to treat metabolic disorders.