霉酚酸酯
医学
毒性
代谢物
霉酚酸
药理学
胆汁酸
骨化三醇受体
胃肠道
维生素
内科学
微生物学
受体
移植
生物
作者
Di Zhang,Wei Lv,Xu Yue,Zijian Zhang,Song Zeng,Weixun Zhang,Lian Gong,Limei Shao,Min Zhang,He Tian,Yingying Liu,Yuxuan Wang,Ling Liu,Xiaopeng Hu
标识
DOI:10.1016/j.ajt.2024.02.029
摘要
Mycophenolate mofetil (MMF) is one of the most used immunosuppressive drugs in organ transplantation, but frequent gastrointestinal (GI) side effects through unknown mechanisms limit its clinical use. Gut microbiota and its metabolites were recently reported to play a vital role in MMF-induced GI toxicity, but the specific mechanism of how they interact with the human body is still unclear. Here, we found that secondary bile acids (BAs), as bacterial metabolites, were significantly reduced by MMF administration in the gut of mice. Microbiome data and fecal microbiota transfer model supported a microbiota-dependent effect on the reduction of secondary BAs. Supplementation of the secondary BA lithocholic acid alleviated MMF-induced weight loss, colonic inflammation, and oxidative phosphorylation damage. Genetic deletion of the vitamin D3 receptor (VDR), which serves as a primary colonic BA receptor, in colonic epithelial cells (VDR
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