Eubacterium coprostanoligenes alleviates chemotherapy-induced intestinal mucositis by enhancing intestinal mucus barrier  

作　　者：Dongsheng Bai Jiawei Zhao Runde Wang Jiaying Du Chen Zhou Chunyang Gu Yuxiang Wang Lulu Zhang Yue Zhao Na Lu 

机构地区：[1]State Key Laboratory of Natural Medicines,Jiangsu Key Laboratory of Carcinogenesis and Intervention,Department of Physiology,School of Basic Medicine and Clinical Pharmacy,China Pharmaceutical University,Nanjing 210009,China [2]Department of Clinical Pharmacology,School of Pharmacy,Nanjing Medical University,Nanjing 211166,China

出　　处：《Acta Pharmaceutica Sinica B》2024年第4期1677-1692,共16页药学学报（英文版）

基　　金：This work was supported by the National Natural Science Foundation of China(No.82373910,82204409);The“Double First-Class”University Project(CPU2022QZ20,China)。

摘　　要：Chemotherapy-induced mucositis represents a severe adverse outcome of cancer treatment,significantly curtailing the efficacy of these treatments and,in some cases,resulting in fatal conse-quences.Despite identifying intestinal epithelial cell damage as a key factor in chemotherapy-induced mucositis,the paucity of effective treatments for such damage is evident.In our study,we discovered that Eubacterium coprostanoligenes promotes mucin secretion by goblet cells,thereby fortifying the integrity of the intestinal mucus barrier.This enhanced barrier function serves to resist microbial invasion and sub-sequently reduces the inflammatory response.Importantly,this effect remains unobtrusive to the anti-tumor efficacy of chemotherapy drugs.Mechanistically,E.copr up-regulates the expression of AUF1,leading to the stabilization of Muc2 mRNA and an increase in mucin synthesis in goblet cells.An espe-cially significant finding is that E.copr activates the AhR pathway,thereby promoting the expression of AUF1.In summary,our results strongly indicate that E.copr enhances the intestinal mucus barrier,effec-tively alleviating chemotherapy-induced intestinal mucositis by activating the AhR/AUFl pathway,consequently enhancing Muc2 mRNA stability.

关 键 词：CHEMOTHERAPY MUCOSITIS Eubacterium coprostanoligenes MUC2 AUF1 

分 类 号：R392[医药卫生—免疫学]