Beneficial Effects of Celastrol on Immune Balance by Modulating Gut Microbiota in Experimental Ulcerative Colitis Mice

作     者：Mingyue Li Weina Guo Yalan Dong Wenzhu Wang Chunxia Tian Zili Zhang Ting Yu Haifeng Zhou Yang Gui Kaming Xue Junyi Li Feng Jiang Alexey Sarapultsev Huafang Wang Ge Zhang Shanshan Luo Heng Fan Desheng Hu Mingyue Li;Weina Guo;Yalan Dong;Wenzhu Wang;Chunxia Tian;Zili Zhang;Ting Yu;Haifeng Zhou;Yang Gui;Kaming Xue;Junyi Li;Feng Jiang;Alexey Sarapultsev;Huafang Wang;Ge Zhang;Shanshan Luo;Heng Fan;Desheng Hu

作者机构：Department of Integrated Traditional Chinese and Western MedicineUnion HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430022China Department of GastroenterologyZhongda HospitalSoutheast UniversityNanjing 210009China Institute of International EducationTianjin University of Traditional Chinese MedicineTianjin 301617China Institute of Immunology and PhysiologyUral Branch of the Russian Academy of SciencesEkaterinburg 620049Russia Institute of HematologyUnion HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430022China Institute of Integrated Bioinfomedicine and Translational ScienceSchool of Chinese MedicineHong Kong Baptist UniversityHong Kong Special Administrative Region 999077China 

出 版 物：《Genomics, Proteomics & Bioinformatics》 (基因组蛋白质组与生物信息学报（英文版）)

年 卷 期：2022年第20卷第2期

页      面：288-303页

核心收录：

学科分类：0710[理学-生物学] 1002[医学-临床医学] 10[医学] 

基　　金：funded by the grants from the National Key R&D Program of China(Grant No.2019YFC1316204) the National Natural Science Foundation of China(Grant Nos.81974249,31770983,82070136,and 82104488) the Hubei Provincial Natural Science Foundation of China(Grant No.2020BHB016). 

主　　题：Ulcerative colitis Celastrol Gut microbiota Treg/Th balance Metabolomics 

摘      要：Ulcerative colitis(UC)is a chronic inflammatory bowel disease caused by many factors including colonic inflammation and microbiota dysbiosis.Previous studies have indicated that celastrol(CSR)has strong anti-inflammatory and immune-inhibitory effects.Here,we investigated the effects of CSR on colonic inflammation and mucosal immunity in an experimental colitis model,and addressed the mechanism by which CSR exerts the protective effects.We characterized the therapeutic effects and the potential mechanism of CSR on treating UC using histological staining,intestinal permeability assay,cytokine assay,flow cytometry,fecal microbiota transplantation(FMT),16S rRNA sequencing,untargeted metabolomics,and cell differentiation.CSR administration significantly ameliorated the dextran sodium sulfate(DSS)-induced colitis in mice,which was evidenced by the recovered body weight and colon length as well as the decreased disease activity index(DAI)score and intestinal permeability.Meanwhile,CSR down-regulated the production of pro-inflammatory cytokines and up-regulated the amount of anti-inflammatory mediators at both mRNA and protein levels,and improved the balances of Treg/Th1 and Treg/Th17 to maintain the colonic immune homeostasis.Notably,all the therapeutic effects were exerted in a gut microbiota-dependent manner.Furthermore,CSR treatment increased the gut microbiota diversity and changed the compositions of the gut microbiota and metabolites,which is probably associated with the gut microbiota-mediated protective effects.In conclusion,this study provides the strong evidence that CSR may be a promising therapeutic drug for UC.