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在克罗恩病肠道组织中丰富,并损害小鼠的愈合。

is enriched in Crohn's disease intestinal tissue and impairs healing in mice.

机构信息

Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.

Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.

出版信息

Science. 2021 Mar 12;371(6534):1154-1159. doi: 10.1126/science.abd0919.

Abstract

Alterations of the mycobiota composition associated with Crohn's disease (CD) are challenging to link to defining elements of pathophysiology, such as poor injury repair. Using culture-dependent and -independent methods, we discovered that preferentially localized to and was abundant within incompletely healed intestinal wounds of mice and inflamed mucosal tissues of CD human subjects. cultures from injured mice and inflamed CD tissues impaired colonic healing when introduced into injured conventionally raised or gnotobiotic mice. We reisolated from injured areas of these mice, fulfilling Koch's postulates. Mechanistically, impaired mucosal healing through the myeloid cell-specific type 1 interferon-CCL5 axis. Taken together, we have identified a fungus that inhabits inflamed CD tissue and can lead to dysregulated mucosal healing.

摘要

与克罗恩病(CD)相关的真菌群落组成的改变难以与病理生理学的明确因素联系起来,例如损伤修复不良。我们使用依赖和不依赖培养的方法发现, 优先定殖于并在未完全愈合的小鼠肠道伤口和 CD 人类受试者的炎症性黏膜组织中丰富存在。从受伤的小鼠和炎症性 CD 组织中分离出来的 培养物在引入受伤的常规饲养或无菌小鼠时会损害结肠愈合。我们从这些小鼠的受伤区域重新分离出 ,满足科赫假设。从机制上讲, 通过髓样细胞特异性 1 型干扰素-CCL5 轴损害黏膜愈合。综上所述,我们已经确定了一种栖息在炎症性 CD 组织中的真菌,它可以导致黏膜愈合失调。

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引用本文的文献

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Gut microbiota-derived metabolites as key actors in inflammatory bowel disease.肠道微生物衍生代谢物作为炎症性肠病的关键因素。
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Microbial genes and pathways in inflammatory bowel disease.炎症性肠病中的微生物基因和途径。
Nat Rev Microbiol. 2019 Aug;17(8):497-511. doi: 10.1038/s41579-019-0213-6.
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Commensal Fungi in Health and Disease.健康与疾病中的共生真菌
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