Comparison of liver bile acid profiles in chronic alcohol feeding and NIAAA binge-on-chronic alcohol feeding mouse models

Alcohol-associated liver disease (ALD) is associated with disturbances in bile acid (BA) metabolism. Several mouse models have been established to mimic human ALD in the clinical setting for mechanistic investigations, and differences in BA metabolism between these models have not been systematically studied. We quantified BA alterations by liquid chromatography-mass spectrometry (LC-MS) in the livers of two widely used mouse models: the chronic Lieber-DeCarli ethanol diet (CLD) model and the National Institute on Alcohol Abuse and Alcoholism binge-on-chronic alcohol feeding (NIAAA) model, both of which aim to mimic the early stages of human ALD. Statistical analysis showed that total BA levels did not change significantly in either model. However, unconjugated BAs were elevated in both models, and glycol-conjugated BAs were significantly increased only in the NIAAA model. The deconjugation capacity of ursodeoxycholic acid (UDCA) and β-muricholic acid (β-MCA) was increased in the CLD model, whereas that of cholic acid (CA) and lithocholic acid (LCA) was increased in the NIAAA model. NIAAA mice showed increased FXR affinity, implying that the classical biosynthetic pathway of hepatic BAs was inhibited. In conclusion, although total BA levels remained unchanged in the early stages of ALD in both models, the BA composition was more altered in the NIAAA model than in the CLD model, suggesting that different ALD mouse models may exhibit divergent regulatory mechanisms for BA metabolism.