Bile Acid Metabolism in Health and Disease

This chapter summarizes the basic knowledge of bile acid chemistry and biology, new mechanistic understanding of the regulation of bile acid homeostasis, human diseases related to altered bile acid metabolism, and the advances in bile acid-based therapies. In hepatocytes, two major bile acid biosynthesis pathways, namely the classic pathway and the alternative pathway, synthesize primary bile acids. Deficiency of primary bile acid synthesis causes malabsorption of fat, steroids, and fat-soluble vitamins, leading to steatorrhea and growth retardation. Hepatic basolateral uptake of bile acids is more active in the periportal hepatocytes rather than the pericentral hepatocytes. Nuclear receptors, the gut microbiota, nutrients, and circadian rhythms control bile acid metabolism and homeostasis. Inborn errors of bile acid metabolism are rare but are usually associated with severe hepatic complications. Studies support the concept of targeting different steps in the enterohepatic circulation of bile acids to achieve therapeutic benefits in various liver and metabolic diseases.