肠道评论衍生琥珀酸盐促进溃疡性结肠炎的结肠炎症。

IF 7.8 1区 生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
Rajdeep Dalal, Srikanth Sadhu, Aashima Batra, Sandeep Goswami, Jyotsna Dandotiya, Vinayakadas K V, Rahul Yadav, Virendra Singh, Kartikey Chaturvedi, Rahul Kannan, Shakti Kumar, Yashwant Kumar, Deepak Kumar Rathore, Deepak B Salunke, Vineet Ahuja, Amit Awasthi
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引用次数: 0

摘要

肠道微生物衍生的代谢物在调节炎症性肠病(IBD)的炎症反应中起着至关重要的作用。在这项研究中,我们发现肠道微生物来源的琥珀酸是溃疡性结肠炎(UC)炎症的驱动因素,通过激活琥珀酸应答的结肠炎辅助T (Th)细胞分泌白细胞介素(IL)-9。我们证明结肠炎与产生琥珀酸的肠道细菌的增加和琥珀酸代谢肠道细菌的减少有关。同样,UC患者表现出产生琥珀酸的肠道细菌和腔内琥珀酸水平升高。产生琥珀酸的肠道细菌或增加琥珀酸可利用性的肠道定植,通过激活结肠源性Th9细胞加剧结肠炎症。相比之下,琥珀酸代谢肠道细菌的肠道定植,用拮抗剂阻断琥珀酸受体信号,或用抗IL-9抗体中和IL-9,通过减少结肠菌源性Th9细胞来减轻炎症。我们的研究结果强调了肠道微生物来源的琥珀酸盐在驱动结肠原性Th9细胞中的作用,并提示其作为治疗IBD的治疗靶点的潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Gut commensals-derived succinate impels colonic inflammation in ulcerative colitis.

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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来源期刊
npj Biofilms and Microbiomes
npj Biofilms and Microbiomes Immunology and Microbiology-Microbiology
CiteScore
12.10
自引率
3.30%
发文量
91
审稿时长
9 weeks
期刊介绍: npj Biofilms and Microbiomes is a comprehensive platform that promotes research on biofilms and microbiomes across various scientific disciplines. The journal facilitates cross-disciplinary discussions to enhance our understanding of the biology, ecology, and communal functions of biofilms, populations, and communities. It also focuses on applications in the medical, environmental, and engineering domains. The scope of the journal encompasses all aspects of the field, ranging from cell-cell communication and single cell interactions to the microbiomes of humans, animals, plants, and natural and built environments. The journal also welcomes research on the virome, phageome, mycome, and fungome. It publishes both applied science and theoretical work. As an open access and interdisciplinary journal, its primary goal is to publish significant scientific advancements in microbial biofilms and microbiomes. The journal enables discussions that span multiple disciplines and contributes to our understanding of the social behavior of microbial biofilm populations and communities, and their impact on life, human health, and the environment.
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