Wu Dandan, Lin Qiwen, Hou Senao, Cui Xiaorui, Shou Na, Yuan Xuefeng, Xu Wenqian, Fu Keyi, Wang Qi, Shi Zunji
State Key Laboratory of Herbage Improvement and Grassland Agro-Ecosystems, Center for Grassland Microbiome, College of Pastoral Agriculture Science and Technology, Lanzhou University, Lanzhou 730000, China.
Int J Mol Sci. 2025 Apr 3;26(7):3332. doi: 10.3390/ijms26073332.
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--muricholic acid (T--MCA) in serum and liver, which was due to the reduction of Lactobacillus spp. A farnesoid X receptor (FXR) antagonist, T--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.
锑和铜会污染蔬菜，并通过消化道进入人体，引发严重且广泛的生物毒性。然而，胆汁酸（BAs）在锑或铜诱发肝脏炎症的发病机制中的作用尚未阐明。我们的结果表明，锑和/或铜会诱发肝脏炎症，导致肠道微生物群紊乱，益生菌下调和有害细菌上调与肝脏炎症密切相关。胆汁酸的靶向代谢组学表明，锑和/或铜显著上调了血清和肝脏中牛磺酸-鼠胆酸（T-MCA）的水平，这是由于乳酸杆菌属的减少所致。一种法尼醇X受体（FXR）拮抗剂，T-MCA抑制肝脏中的FXR-SHP途径和回肠中的FXR-FGF15途径，从而促进胆固醇7-α羟化酶（CYP7A1）的转录并增加总胆汁酸浓度，最终导致肝脏炎症。这些发现为锑和/或铜诱发肝脏炎症的潜在机制提供了新的见解。
