Multiple roles of bile acids in ferroptosis regulation: Opportunities for disease therapy

Bile acids (BAs), the main component of bile, play a key role in the digestion of lipids. However, recent studies have demonstrated that BAs can also act as signaling molecules, regulating metabolism by binding to BA receptors. Ferroptosis is an iron-dependent form of cell death characterized by lipid peroxidation, and it is closely associated with lipid and iron metabolism. Recent studies have shown that BA levels are significantly correlated with ferroptosis in certain diseases, including liver and gallbladder diseases, colitis, tumors, and infectious diseases. However, the effect of BAs on ferroptosis varies. Some BAs, such as deoxycholic acid (DCA), glycochenodeoxycholic acid (GCDCA), and ursodeoxycholic acid (UDCA), can trigger cellular oxidative stress, which, in turn, induces ferroptosis. While other BAs, such as taurolithocholic acid (TLCA) and tauroursodeoxycholic acid (TUDCA), significantly inhibit ferroptosis, thereby attenuating cell and tissue damage. To our knowledge, this review is the first to systematically summarize the roles and mechanisms of BAs in regulating ferroptosis under different disease conditions. Potential therapeutic methods and clinical applications have also been proposed for targeting BA-mediated ferroptosis in various diseases, providing guidance for subsequent research on BAs and ferroptosis.