Reference - Detail
| RRC ID | 89047 |
|---|---|
| Author | Dalal R, Sadhu S, Batra A, Goswami S, Dandotiya J, K V V, Yadav R, Singh V, Chaturvedi K, Kannan R, Kumar S, Kumar Y, Rathore DK, Salunke DB, Ahuja V, Awasthi A. |
| Title | Gut commensals-derived succinate impels colonic inflammation in ulcerative colitis. |
| Journal | NPJ Biofilms Microbiomes |
| Abstract |
Gut microbiota-derived metabolites play a crucial role in modulating the inflammatory response in inflammatory bowel disease (IBD). In this study, we identify gut microbiota-derived succinate as a driver of inflammation in ulcerative colitis (UC) by activating succinate-responsive, colitogenic helper T (Th) cells that secrete interleukin (IL)-9. We demonstrate that colitis is associated with an increase in succinate-producing gut bacteria and decrease in succinate-metabolizing gut bacteria. Similarly, UC patients exhibit elevated levels of succinate-producing gut bacteria and luminal succinate. Intestinal colonization by succinate-producing gut bacteria or increased succinate availability, exacerbates colonic inflammation by activating colitogenic Th9 cells. In contrast, intestinal colonization by succinate-metabolizing gut bacteria, blocking succinate receptor signaling with an antagonist, or neutralizing IL-9 with an anti-IL-9 antibody alleviates inflammation by reducing colitogenic Th9 cells. Our findings underscore the role of gut microbiota-derived succinate in driving colitogenic Th9 cells and suggesting its potential as a therapeutic target for treating IBD. |
| Volume | 11(1) |
| Pages | 44 |
| Published | 2025-3-13 |
| DOI | 10.1038/s41522-025-00672-3 |
| PII | 10.1038/s41522-025-00672-3 |
| PMID | 40082467 |
| PMC | PMC11906746 |
| MeSH | Animals Bacteria* / classification Bacteria* / genetics Bacteria* / isolation & purification Bacteria* / metabolism Colitis, Ulcerative* / immunology Colitis, Ulcerative* / microbiology Colitis, Ulcerative* / pathology Colon* / immunology Colon* / microbiology Colon* / pathology Female Gastrointestinal Microbiome* Humans Inflammation Interleukin-9 / immunology Interleukin-9 / metabolism Male Mice Mice, Inbred C57BL Succinic Acid* / metabolism T-Lymphocytes, Helper-Inducer / immunology |
| Altmetric score |
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 20 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| General Microbes | JCM5826 JCM16074 JCM30894 JCM15077 JCM17568 |