ADT-OH improves intestinal barrier function and remodels the gut microbiota in DSS-induced colitis.
10.1007/s11684-023-0990-1
- Author:
Zhiqian BI
1
;
Jia CHEN
1
;
Xiaoyao CHANG
1
;
Dangran LI
1
;
Yingying YAO
1
;
Fangfang CAI
1
;
Huangru XU
1
;
Jian CHENG
2
;
Zichun HUA
3
;
Hongqin ZHUANG
4
Author Information
1. The State Key Laboratory of Pharmaceutical Biotechnology, College of Life Sciences, Nanjing University, Nanjing, 210023, China.
2. Institute of Neuroscience, Soochow University, Suzhou, 215123, China. jiancheng8@hotmail.com.
3. The State Key Laboratory of Pharmaceutical Biotechnology, College of Life Sciences, Nanjing University, Nanjing, 210023, China. hzc1117@nju.edu.cn.
4. The State Key Laboratory of Pharmaceutical Biotechnology, College of Life Sciences, Nanjing University, Nanjing, 210023, China. hqzhuang@nju.edu.cn.
- Publication Type:Journal Article
- Keywords:
ADT-OH;
gut microbiota;
inflammatory bowel disease;
intestinal permeability
- MeSH:
Humans;
Mice;
Animals;
Gastrointestinal Microbiome;
Intestinal Barrier Function;
Mice, Inbred C57BL;
Colitis/metabolism*;
Inflammatory Bowel Diseases/drug therapy*;
Inflammation;
Anti-Inflammatory Agents/pharmacology*;
Disease Models, Animal
- From:
Frontiers of Medicine
2023;17(5):972-992
- CountryChina
- Language:English
-
Abstract:
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 H2S 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.
