ADT-OH improves intestinal barrier function and remodels the gut microbiota in DSS-induced colitis  

作　　者：Zhiqian Bi Jia Chen Xiaoyao Chang Dangran Li Yingying Yao Fangfang Cai Huangru Xu Jian Cheng Zichun Hua Hongqin Zhuang 

机构地区：[1]The State Key Laboratory of Pharmaceutical Biotechnology,College of Life Sciences,Nanjing University,Nanjing,210023,China [2]Changzhou High-Tech Research Institute of Nanjing University and Jiangsu TargetPharma Laboratories Inc.,Changzhou,213164,China [3]School of Biopharmacy,China Pharmaceutical University,Nanjing,211198,China [4]Institute of Neuroscience,Soochow University,Suzhou,215123,China

出　　处：《Frontiers of Medicine》2023年第5期972-992,共21页医学前沿（英文版）

基　　金：supported by grants from the National Natural Science Foundation of China (Nos.82130106 and 32250016);Nanjing Special Fund for Life and Health Science and Technology (No.202110016);Changzhou Municipal Department of Science and Technology (Nos.CZ20210010,CJ20210024,and CJ20220019).

摘　　要：Owing to the increasing incidence and prevalence of inflammatory bowel disease(IBD)worldwide,effective and safe treatments for IBD are urgently needed.Hydrogen sulfide(H2S)is an endogenous gasotransmitter and plays an important role in inflammation.To date,H2S-releasing agents are viewed as potential anti-inflammatory drugs.The slow-releasing H_(2)S donor 5-(4-hydroxyphenyl)-3H-1,2-dithiole-3-thione(ADT-OH),known as a potent therapeutic with chemopreventive and cytoprotective properties,has received attention recently.Here,we reported its anti-inflammatory effects on dextran sodium sulfate(DSS)-induced acute(7 days)and chronic(30 days)colitis.We found that ADT-OH effectively reduced the DSS-colitis clinical score and reversed the inflammation-induced shortening of colon length.Moreover,ADT-OH reduced intestinal inflammation by suppressing the nuclear factor kappa-B pathway.In vivo and in vitro results showed that ADT-OH decreased intestinal permeability by increasing the expression of zonula occludens-1 and occludin and blocking increases in myosin II regulatory light chain phosphorylation and epithelial myosin light chain kinase protein expression levels.In addition,ADT-OH restored intestinal microbiota dysbiosis characterized by the significantly increased abundance of Muribaculaceae and Alistipes and markedly decreased abundance of Helicobacter,Mucispirillum,Parasutterella,and Desulfovibrio.Transplanting ADT-OH-modulated microbiota can alleviate DSS-induced colitis and negatively regulate the expression of local and systemic proinflammatory cytokines.Collectively,ADT-OH is safe without any short-term(5 days)or long-term(30 days)toxicological adverse effects and can be used as an alternative therapeutic agent for IBD treatment.

关 键 词：inflammatory bowel disease ADT-OH intestinal permeability gut microbiota 

分 类 号：R574[医药卫生—消化系统]