GLP ‐1 receptor agonists alleviate colonic inflammation by modulating intestinal microbiota and the function of group 3 innate lymphoid cells
Open accessAbstract
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 RORgt gfp/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.
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GLP-1RA-induced delayed gastric emptying and gut microbiota modulation may alter micronutrient metabolism and absorption, though direct evidence of clinically significant deficiencies is limited.
“GLP-1RA-induced delayed gastric emptying and gut microbiota modulation may alter micronutrient metabolism and absorption, though direct evidence of clinically significant deficiencies is limited [43].”
From Nutritional deficiencies and muscle loss in adults with type 2 diabetes using GLP-1 receptor agonists: A retrospective observational study (2025) · cites this paper as [43]
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Effects of GLP-1 Analogues and Agonists on the Gut Microbiota: A Systematic Review
Gofron, K. K., Wasilewski, A., & Małgorzewicz, S. (2025) · Nutrients · doi:10.3390/nu17081303 · Cited by 90 · see citing works
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“GLP-1RA-induced delayed gastric emptying and gut microbiota modulation may alter micronutrient metabolism and absorption, though direct evidence of clinically significant deficiencies is limited [43].”
Gong, B., Li, C., Shi, Z., Wang, F., Dai, R., Chen, G., & Su, H. (2025) · Frontiers in Pharmacology · doi:10.3389/fphar.2025.1675552 · Cited by 36 · see citing works
- Authors
- Sun, H., Shu, J., Tang, J., Li, Y., Qiu, J., Ding, Z., Xuan, B., Chen, M., Gan, C., Lin, J., Qiu, J., Sheng, H., & Wang, C.
- Affiliations
- Shanghai Jiao Tong University (CN)
- Shanghai Institute of Nutrition and Health (CN)
- Second Hospital of Shandong University (CN)
- Corresponding author
- Qiu, Ju
- Sheng, Huiming
- Wang, Chuanxin
- Venue
- Immunology
- Publisher
- Wiley
- Published
- 2024-03-27
- Volume
- 172
- Issue
- 3
- Pages
- 451-468
- ISSN
- 0019-2805 (ISSN-L)
- 1365-2567
- OpenAlex
- W4393270487
- Cited by
- 54
- References
- 50
- Citations by year
- 2026: 27 · 2025: 25 · 2024: 2
- FWCI
- 14.33
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81702071, 82070730)
- Science and Technology Commission of Shanghai Municipality (22ZR1481800)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
- Life Sciences › Immunology and Microbiology › Immunology › IL-33, ST2, and ILC Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Keywords
- GLP-1 receptor agonists, colitis, inflammatory bowel disease, ILC3, IL-22, gut microbiota, DSS-induced colitis, N,N-dimethylsphingosine, Lactobacillus reuteri, RORγt, type 2 diabetes complications
- MeSH terms
- Glucagon-Like Peptide-1 Receptor, Gastrointestinal Microbiome, Liraglutide, Interleukin-22, Glucagon-Like Peptide-1 Receptor Agonists, Animals, Colitis, Colon, Disease Models, Animal, Immunity, Innate, Interleukins, Lymphocytes, Mice, Inbred C57BL, Dextran Sulfate, Mice, Knockout, Mice
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