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肠道微生物群在炎症性肠病发病机制中的作用:过去十年我们学到了什么?

Role of the gut microbiota in inflammatory bowel disease pathogenesis: what have we learnt in the past 10 years?

作者信息

Hold Georgina L, Smith Megan, Grange Charlie, Watt Euan Robert, El-Omar Emad M, Mukhopadhya Indrani

机构信息

Georgina L Hold, Megan Smith, Charlie Grange, Euan Robert Watt, Emad M El-Omar, Indrani Mukhopadhya, Gastrointestinal Research Group, Division of Applied Medicine, University of Aberdeen, Foresterhill, Aberdeen AB252ZD, United Kingdom.

出版信息

World J Gastroenterol. 2014 Feb 7;20(5):1192-210. doi: 10.3748/wjg.v20.i5.1192.

Abstract

Our understanding of the microbial involvement in inflammatory bowel disease (IBD) pathogenesis has increased exponentially over the past decade. The development of newer molecular tools for the global assessment of the gut microbiome and the identification of nucleotide-binding oligomerization domain-containing protein 2 in 2001 and other susceptibility genes for Crohn's disease in particular has led to better understanding of the aetiopathogenesis of IBD. The microbial studies have elaborated the normal composition of the gut microbiome and its perturbations in the setting of IBD. This altered microbiome or "dysbiosis" is a key player in the protracted course of inflammation in IBD. Numerous genome-wide association studies have identified further genes involved in gastrointestinal innate immunity (including polymorphisms in genes involved in autophagy: ATG16L1 and IGRM), which have helped elucidate the relationship of the local innate immunity with the adjacent luminal bacteria. These developments have also spurred the search for specific pathogens which may have a role in the metamorphosis of the gut microbiome from a symbiotic entity to a putative pathogenic one. Here we review advances in our understanding of microbial involvement in IBD pathogenesis over the past 10 years and offer insight into how this will shape our therapeutic management of the disease in the coming years.

摘要

在过去十年中,我们对微生物在炎症性肠病(IBD)发病机制中的作用的理解呈指数级增长。用于全面评估肠道微生物群的更新分子工具的发展,以及2001年核苷酸结合寡聚化结构域含蛋白2和特别是克罗恩病其他易感基因的鉴定,使我们对IBD的病因发病机制有了更好的理解。微生物研究阐述了肠道微生物群的正常组成及其在IBD情况下的扰动。这种改变的微生物群或“生态失调”是IBD炎症迁延过程中的关键因素。大量全基因组关联研究确定了更多参与胃肠道固有免疫的基因(包括自噬相关基因:ATG16L1和IGRM中的多态性),这有助于阐明局部固有免疫与相邻管腔细菌之间的关系。这些进展也促使人们寻找可能在肠道微生物群从共生实体转变为假定致病实体的过程中起作用的特定病原体。在此,我们回顾过去10年我们对微生物在IBD发病机制中的作用的理解的进展,并深入探讨这将如何在未来几年塑造我们对该疾病的治疗管理。

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