期刊
FRONTIERS IN IMMUNOLOGY
卷 11, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2020.585431
关键词
IBD; IL-10; enterobacteriaceae; colitis; microbiome; temporal dynamic changes; dysbiosis; cytokine response
类别
资金
- Iowa State University, College of Veterinary Medicine and Graduate College
- National Institute of General Medicine [R01GM099537]
Research shows that the composition of the cecal microbiota in IL-10(-/-) mice changes as inflammation progresses, leading to a biphasic progression in disease severity. While the overall diversity of the microbiota is similar in young mice, IL-10(-/-) mice fail to increase in complexity as they mature.
The intestinal microbiota is a critical component of mucosal health as evidenced by the fact that alterations in the taxonomic composition of the gastrointestinal microbiota are associated with inflammatory bowel diseases. To better understand how the progression of inflammation impacts the composition of the gastrointestinal microbiota, we used culture independent taxonomic profiling to identify temporal changes in the cecal microbiota of C3Bir IL-10(-/-) mice concomitantly with the onset and progression of colitis. This analysis revealed that IL-10(-/-) mice displayed a biphasic progression in disease severity, as evidenced by histopathological scores and cytokine production. Beginning at 4 weeks of age, pro-inflammatory cytokines including TNF-alpha, IFN-gamma, IL-6, G-CSF, and IL-1 alpha as well as chemokines including RANTES and MIP-1 alpha were elevated in the serum of IL-10(-/-) mice. By 19 weeks of age, the mice developed clinical signs of disease as evidenced by weight loss, which was accompanied by a significant increase in serum levels of KC and IL-17. While the overall diversity of the microbiota of both wild type and IL-10(-/-) were similar in young mice, the latter failed to increase in complexity as the mice matured and experienced changes in abundance of specific bacterial taxa that are associated with inflammatory bowel disease in humans. Collectively, these results reveal that there is a critical time in young mice between four to six weeks of age when inflammation and the associated immune responses adversely affect maturation of the microbiota.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据