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Here, we report that GLP\u20101RAs ameliorate dextran sulfate sodium (DSS)\u2010induced colitis in both wild\u2010type and T\/B\u2010cell\u2010deficient mice through modulating group 3 innate lymphoid cells (ILC3s), a subset of innate lymphoid cells that regulate intestinal immunity. GLP\u20101RAs promote IL\u201022 production by ILC3, and the protective effect of GLP\u20101RAs on DSS\u2010induced colitis was abrogated in ILC3\u2010deficient\n                    <jats:italic>RORgt<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>gfp\/gfp<\/jats:italic>\n                    <\/jats:sup>\n                    mice. Furthermore, the treatment effect of GLP\u2010RAs on colitis, as well as the generation of IL\u201022\u2010producing ILC3s by GLP\u2010RAs, is dependent on the gut microbiota. GLP\u20101RAs increase the abundance of\n                    <jats:italic>Firmicutes<\/jats:italic>\n                    and\n                    <jats:italic>Proteobacteria<\/jats:italic>\n                    in the gut, particularly beneficial bacteria such as\n                    <jats:italic>Lactobacillus reuteri,<\/jats:italic>\n                    and decrease the abundance of enteropathogenic\n                    <jats:italic>Staphylococcus<\/jats:italic>\n                    bacteria. The untargeted gas chromatography (GC)\/liquid chromatography (LC)\u2010mass spectrometry (MS) of faecal metabolites further revealed enrichment of N,N\u2010dimethylsphingosine (DMS), an endogenous metabolite derived from sphingosine, in the GLP\u20101RA\u2010treated group. Strikingly, DMS ameliorates colitis while promoting intestinal IL\u201022\u2010producing ILC3s. Taken together, our findings show that GLP\u20101RAs exert a therapeutic effect on colitis possibly by regulating the microbiota\u2010DMS\u2010IL\u201022\n                    <jats:sup>+<\/jats:sup>\n                    ILC3 axis, highlighting the potential beneficial role of GLP\u2010RAs in inflammatory intestinal disorders with diabetes complications.\n                  <\/jats:p>","DOI":"10.1111\/imm.13784","type":"journal-article","created":{"date-parts":[[2024,3,28]],"date-time":"2024-03-28T02:59:49Z","timestamp":1711594789000},"page":"451-468","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":57,"title":["<scp>GLP<\/scp>\n                    \u20101 receptor agonists alleviate colonic inflammation by modulating intestinal microbiota and the function of group 3 innate lymphoid 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