Gut Microbiota and Its Metabolite Taurine-β-Muricholic Acid Contribute to Antimony- and/or Copper-Induced Liver...

Antimony and copper can contaminate vegetables and enter the human body through the digestive tract, inducing severe and extensive biotoxicity. However, the role of bile acids (BAs) in the pathogenesis of liver inflammation by antimony or copper has not been elucidated. Our results indicated that antimony and/or copper induced liver inflammation, causing the disruption of gut microbiota, with the down-regulation of probiotics and up-regulation of harmful bacteria closely correlated to liver inflammation. Targeted metabolomics of BAs showed that antimony and/or copper significantly up-regulated the levels of taurine-β-muricholic acid (T-β-MCA) in serum and liver, which was due to the reduction of Lactobacillus spp. A farnesoid X receptor (FXR) antagonist, T-β-MCA inhibited the FXR-SHP pathway in liver and FXR-FGF15 pathway in ileum, thereby promoting the transcription of cholesterol 7-alpha hydroxylase (CYP7A1) and increasing total bile acid concentrations, ultimately leading to liver inflammation. These findings provide new insights into the underlying mechanisms of antimony- and/or copper-induced liver inflammation.