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Methionine-choline deficient diet deteriorates DSS-induced murine colitis through disturbance of gut microbes and infiltration of macrophages

文献类型：期刊论文

作者Liu, Mo-ting2,3; Zhang, Yao1; Xiang, Cai-gui2,3; Yang, Tao2,3; Wang, Xiao-han2,3; Lu, Qiu-kai2,3; Lu, Hui-min2,3; Fan, Chen3; Feng, Chun-lan3; Yang, Xiao-qian3
刊名ACTA PHARMACOLOGICA SINICA
出版日期2024-04-29
页码14
关键词ulcerative colitis dyslipidemia methionine-choline deficient diet macrophages gut microbes fecal microbiota transplantation
ISSN号1671-4083
DOI10.1038/s41401-024-01291-y
通讯作者Zou, Duo-wu(zdw12125@rjh.com.cn) ; Li, Heng(cpuliheng@126.com) ; Tang, Wei(tangwei@simm.ac.cn)
英文摘要Ulcerative colitis (UC) is associated with changed dietary habits and mainly linked with the gut microbiota dysbiosis, necroptosis of epithelial cells, and mucosal ulcerations. Liver dysfunction and abnormal level of liver metabolism indices were identified in UC patients, suggesting a close interaction between gut and liver disorders. Methionine-choline deficient diet (MCD) has been shown to induce persistent alterations of gut microbiota and metabolome during hepatitis. In this study we further explored the disease phenotypes in UC patients and investigated whether MCD functioned as a trigger for UC susceptibility. After assessing 88 serum specimens from UC patients, we found significant liver dysfunction and dyslipidemia including abnormal ALT, AST, TG, TC, LDL-c and HDL-c. Liver dysfunction and dyslipidemia were confirmed in DSS-induced colitis mice. We fed mice with MCD for 14 days to cause mild liver damage, and then treated with DSS for 7 days. We found that MCD intake significantly exacerbated the pathogenesis of mucosal inflammation in DSS-induced acute, progressive, and chronic colitis, referring to promotion of mucosal ulcers, colon shortening, diarrhea, inflammatory immune cell infiltration, cytokines release, and abnormal activation of inflammatory macrophages in colon and liver specimens. Intraperitoneal injection of clodronate liposomes to globally delete macrophages dramatically compromised the pathogenesis of MCD-triggering colitis. In addition, MCD intake markedly changed the production pattern of short-chain fatty acids (SCFAs) in murine stools, colons, and livers. We demonstrated that MCD-induced colitis pathogenesis largely depended on the gut microbes and the disease phenotypes could be transmissible through fecal microbiota transplantation (FMT). In conclusion, this study supports the concept that intake of MCD predisposes to experimental colitis and enhances its pathogenesis via modulating gut microbes and macrophages in mice.
WOS关键词ULCERATIVE-COLITIS ; DISEASE ; MANIFESTATIONS ; METABOLITES ; FOOD
资助项目National Natural Science Foundation of China[82173822]
WOS研究方向Chemistry ; Pharmacology & Pharmacy
语种英语
WOS记录号WOS:001209627800005
出版者NATURE PUBL GROUP
源URL[http://119.78.100.183/handle/2S10ELR8/310989]  
专题中国科学院上海药物研究所
通讯作者Zou, Duo-wu; Li, Heng; Tang, Wei
作者单位1.Shanghai Jiao Tong Univ, Ruijin Hosp, Sch Med, Dept Gastroenterol, Shanghai 200025, Peoples R China
2.Univ Chinese Acad Sci, Sch Pharm, Beijing 100049, Peoples R China
3.Chinese Acad Sci, Shanghai Inst Mat Med, Lab Antiinflammat & Immunopharmacol, State Key Lab Chem Biol, Shanghai 201203, Peoples R China
推荐引用方式
GB/T 7714		 Liu, Mo-ting,Zhang, Yao,Xiang, Cai-gui,et al. Methionine-choline deficient diet deteriorates DSS-induced murine colitis through disturbance of gut microbes and infiltration of macrophages[J]. ACTA PHARMACOLOGICA SINICA,2024:14.
APA Liu, Mo-ting.,Zhang, Yao.,Xiang, Cai-gui.,Yang, Tao.,Wang, Xiao-han.,...&Tang, Wei.(2024).Methionine-choline deficient diet deteriorates DSS-induced murine colitis through disturbance of gut microbes and infiltration of macrophages.ACTA PHARMACOLOGICA SINICA,14.
MLA Liu, Mo-ting,et al."Methionine-choline deficient diet deteriorates DSS-induced murine colitis through disturbance of gut microbes and infiltration of macrophages".ACTA PHARMACOLOGICA SINICA (2024):14.

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来源：上海药物研究所

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