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GLP-1 receptor agonists alleviate colonic inflammation by modulating intestinal microbiota and the function of group 3 innate lymphoid cells

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WOS体系：
Pubmed体系：

收录情况： ◇ SCIE

作者：
Sun Hanxiao[1,2] * ; Shu Jie[2] * ; Tang Jupei[3] ; Li Yue[2] ; Qiu Jinxin[3] ; Ding Zhaoyun[3] ; Xuan Binbin[2] ; Chen Minghui[2] ; Gan Chenxin[2] ; Lin Jinpiao[2] ; Qiu Ju[3,*1] ; Sheng Huiming[2,*2] ; Wang Chuanxin[1,*3] ;
机构： [1]Department of Clinical Laboratory, The Second Hospital of Shandong University, Jinan, Shandong, China. [2]Department of Laboratory Medicine, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. [3]CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
出处：
DOI： 10.1111/imm.13784
ISSN：

关键词： colitis glucagon-like peptide 1 receptor agonists (GLP-1RAs) group 3 innate lymphoid cells (ILC3s) gut microbiome N N-dimethylsphingosine (DMS)

摘要：
Glucagon-like peptide-1 receptor agonists (GLP-1RAs), which are drugs used for treating type 2 diabetes, have been reported to exert anti-inflammatory effects on inflammatory bowel disease (IBD), the mechanism of which remains elusive. Here, we report that GLP-1RAs ameliorate dextran sulfate sodium (DSS)-induced colitis in both wild-type and T/B-cell-deficient mice through modulating group 3 innate lymphoid cells (ILC3s), a subset of innate lymphoid cells that regulate intestinal immunity. GLP-1RAs promote IL-22 production by ILC3, and the protective effect of GLP-1RAs on DSS-induced colitis was abrogated in ILC3-deficient RORgtgfp/gfp mice. Furthermore, the treatment effect of GLP-RAs on colitis, as well as the generation of IL-22-producing ILC3s by GLP-RAs, is dependent on the gut microbiota. GLP-1RAs increase the abundance of Firmicutes and Proteobacteria in the gut, particularly beneficial bacteria such as Lactobacillus reuteri, and decrease the abundance of enteropathogenic Staphylococcus bacteria. The untargeted gas chromatography (GC)/liquid chromatography (LC)-mass spectrometry (MS) of faecal metabolites further revealed enrichment of N,N-dimethylsphingosine (DMS), an endogenous metabolite derived from sphingosine, in the GLP-1RA-treated group. Strikingly, DMS ameliorates colitis while promoting intestinal IL-22-producing ILC3s. Taken together, our findings show that GLP-1RAs exert a therapeutic effect on colitis possibly by regulating the microbiota-DMS-IL-22+ILC3 axis, highlighting the potential beneficial role of GLP-RAs in inflammatory intestinal disorders with diabetes complications.© 2024 John Wiley & Sons Ltd.

基金：
National Natural Science Foundation of China, Grant/Award Numbers: 81702071, 82070730; Shanghai Outstanding Academic Leader Science and Technology Program, Grant/Award Number: 21XD1403000; Changning District Master Doctor Innovative Talent Base, Grant/Award Number: RCJD2021B01; Shanghai Jiao Tong University Key Project of Medical Engineering, Grant/Award Number: YG2021ZD33; Project of Changning District Health Commission,Grant/Award Number: 20234Y003; Youth Project of Changning District Health Commission, Grant/Award Number: 2022QN02; Firefly Project Plan of Tongren Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Grant/Award Number: TRYXJH04; Shanghai Science and Technology Committee (STCSM), Grant/Award Number: 22ZR1481800
语种：
外文
被引次数：
WOS：
PubmedID：
中科院(CAS)分区：
出版当年[2023]版：
大类 | 3 区 医学
小类 | 3 区 免疫学
最新[2025]版：
大类 | 3 区 医学
小类 | 3 区 免疫学
JCR分区：
出版当年[2022]版：
Q2 IMMUNOLOGY
最新[2023]版：
Q2 IMMUNOLOGY

影响因子： 最新[2023版] 最新五年平均 出版当年[2022版] 出版当年五年平均 出版前一年[2021版] 出版后一年[2023版]

第一作者：
第一作者机构： [1]Department of Clinical Laboratory, The Second Hospital of Shandong University, Jinan, Shandong, China. [2]Department of Laboratory Medicine, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
共同第一作者：
通讯作者：
通讯机构： [1]Department of Clinical Laboratory, The Second Hospital of Shandong University, Jinan, Shandong, China. [2]Department of Laboratory Medicine, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. [3]CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China. [*1]CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China. [*2]Department of Laboratory Medicine, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, 1111 Xian Xia Rd, Shanghai 200336, China [*3]Department of Clinical Laboratory, The Second Hospital of Shandong University, Jinan, Shandong 250033, China.
推荐引用方式(GB/T 7714)：
Sun Hanxiao,Shu Jie,Tang Jupei,et al.GLP-1 receptor agonists alleviate colonic inflammation by modulating intestinal microbiota and the function of group 3 innate lymphoid cells[J].IMMUNOLOGY.2024,172(3):451-468.doi:10.1111/imm.13784.
APA：
Sun Hanxiao,Shu Jie,Tang Jupei,Li Yue,Qiu Jinxin...&Wang Chuanxin.(2024).GLP-1 receptor agonists alleviate colonic inflammation by modulating intestinal microbiota and the function of group 3 innate lymphoid cells.IMMUNOLOGY,172,(3)
MLA：
Sun Hanxiao,et al."GLP-1 receptor agonists alleviate colonic inflammation by modulating intestinal microbiota and the function of group 3 innate lymphoid cells".IMMUNOLOGY 172..3(2024):451-468

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