Gut commensals-derived succinate impels colonic inflammation in ulcerative colitis.

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Tác giả: Vineet Ahuja, Amit Awasthi, Aashima Batra, Kartikey Chaturvedi, Rajdeep Dalal, Jyotsna Dandotiya, Sandeep Goswami, Vinayakadas K V, Rahul Kannan, Shakti Kumar, Yashwant Kumar, Deepak Kumar Rathore, Srikanth Sadhu, Deepak B Salunke, Virendra Singh, Rahul Yadav

Ngôn ngữ: eng

Ký hiệu phân loại: 780 Music

Thông tin xuất bản: United States : NPJ biofilms and microbiomes , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 711450

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.
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