| RRC ID |
89047
|
| 著者 |
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.
|
| タイトル |
Gut commensals-derived succinate impels colonic inflammation in ulcerative colitis.
|
| ジャーナル |
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.
|
| 巻・号 |
11(1)
|
| ページ |
44
|
| 公開日 |
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
|
| リソース情報 |
| 一般微生物 |
JCM5826
JCM16074
JCM30894
JCM15077
JCM17568 |
