Elevated systemic total bile acids escalate susceptibility to alcohol-associated liver disease

Excessive alcohol consumption is a major global health problem. Individuals with alcoholic liver disease often exhibit elevated serum total bile acids (TBAs). Nevertheless, the extent to which high TBA contributes to alcohol-associated liver disease (AALD) remains elusive. To investigate this, wild-type mice were categorized into normal (nTBA) and high (hTBA) TBA groups. Both groups underwent chronic-binge ethanol feeding for 4 weeks, followed by additional weekly ethanol doses. Ethanol feeding worsened AALD in both male and female mice with elevated serum TBA, characterized by liver dysfunction and steatosis. Decreased hepatic expression of genes involved in mitochondrial β-oxidation and lipid transport in ethanol-fed hTBA mice suggests that altered fatty acid metabolism contributed to AALD. Our findings, which represent the first to link high serum TBA to increased AALD susceptibility, underscore the importance of proactive serum TBA screening as a valuable tool for identifying individuals at high risk of developing AALD.