The molecular insights of bile acid homeostasis in host diseases

Abstract

Bile acids (BAs) function as detergents promoting nutrient absorption and as hormones regulating nutrient metabolism. Most BAs are key regulatory factors of physiological activities, which are involved in the regulation of glucose, lipid, and drug metabolisms. Hepatic and intestinal diseases have close connections with the systemic cycling disorders of BAs. The abnormal in BA absorption came up with overmuch BAs could be involved in the pathophysiology of liver and bowel and metabolic disorders such as fatty liver diseases and inflammatory bowel diseases. The primary BAs (PBAs), which are synthesized in the liver, can be transformed into the secondary BAs (SBAs) by gut microbiota. The transformation processes are tightly associated with the gut microbiome and the host endogenous metabolism. The BA biosynthesis gene cluster bile-acid-inducible operon is essential for modulating BA pool, gut microbiome composition, and the onset of intestinal inflammation. This forms a bidirectional interaction between the host and its gut symbiotic ecosystem. The subtle changes in the composition and abundance of BAs perturb the host physiological and metabolic activity. Therefore, maintaining the homeostasis of BAs pool contributes to the balance of the body's physiological and metabolic system. Our review aims to dissect the molecular mechanisms underlying the BAs homeostasis, assess the key factors sustaining the homeostasis and the role of BA acting on host diseases. By linking the BAs metabolic disorders and their associated diseases, we illustrate the effects of BAs homeostasis on health and potential clinical interventions can be taken under the latest research findings.

Keywords: Bile acids; Gut microbiome; Homeostasis; Host diseases; Metabolic pathway; Physiological activity.