Regulation of bile acids homeostasis: a feasible and versatile way to treat or diagnose liver disorders

Homeostatic imbalance of bile acids (BAs) is closely associated with the onset and progression of several liver diseases, including cholestasis, hepatic fibrosis, cirrhosis, hepatocellular carcinoma, and MASLD/MASH. In cholestasis, BAs imbalance induces cellular endoplasmic reticulum stress and mitochondrial dysfunction, which subsequently lead to hepatocellular and cholangiocellular death, exacerbating liver injury. Bile acid imbalance also activates hepatic stellate cells, promoting fibrosis and cirrhosis. During hepatocellular carcinoma development and progression, BAs imbalance favors the survival and proliferation of cancerous hepatocytes. Similarly, in MASLD/MASH, homeostatic BAs imbalance correlates significantly with disease severity. Additionally, BAs, through crosstalk with gut microbes, plays a key role in the development and progression of various liver diseases. This review focuses on each liver disease, summarizing the unique changes in BAs species and their distinct mechanisms of action, while exploring the complex role of BAs throughout the course of liver disease and their potential as diagnostic markers. Importantly, it highlights the therapeutic significance of regulating BA homeostasis in treating liver diseases.