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肠道微生物群与肠上皮细胞通透性。

Gut Microbiota and Intestinal Trans-Epithelial Permeability.

机构信息

Centre Nutrition, Santé et Société (NUTRISS), Institut sur la Nutrition et les Aliments Fonctionnels (INAF), Université Laval, Québec, QC G1V 0A6, Canada.

Canada Research Excellence Chair in the Microbiome-Endocannabinoidome Mediators Axis in Metabolic Health (CERC-MEND), Université Laval, Québec, QC G1V 0A6, Canada.

出版信息

Int J Mol Sci. 2020 Sep 3;21(17):6402. doi: 10.3390/ijms21176402.

Abstract

Constant remodeling of tight junctions to regulate trans-epithelial permeability is essential in maintaining intestinal barrier functions and thus preventing diffusion of small molecules and bacteria to host systemic circulation. Gut microbiota dysbiosis and dysfunctional gut barrier have been correlated to a large number of diseases such as obesity, type 2 diabetes and inflammatory bowel disease. This led to the hypothesis that gut bacteria-epithelial cell interactions are key regulators of epithelial permeability through the modulation of tight junctions. Nevertheless, the molecular basis of host-pathogen interactions remains unclear mostly due to the inability of most in vitro models to recreate the differentiated tissue structure and components observed in the normal intestinal epithelium. Recent advances have led to the development of a novel cellular model derived from intestinal epithelial stem cells, the so-called organoids, encompassing all epithelial cell types and reproducing physiological properties of the intestinal tissue. We summarize herein knowledge on molecular aspects of intestinal barrier functions and the involvement of gut bacteria-epithelial cell interactions. This review also focuses on epithelial organoids as a promising model for epithelial barrier functions to study molecular aspects of gut microbiota-host interaction.

摘要

紧密连接的持续重塑对于调节上皮细胞通透性至关重要,这对于维持肠道屏障功能从而防止小分子和细菌扩散到宿主全身循环至关重要。肠道微生物失调和肠道屏障功能障碍与许多疾病相关,如肥胖症、2 型糖尿病和炎症性肠病。这就提出了一个假设,即肠道细菌-上皮细胞相互作用是通过调节紧密连接来调节上皮细胞通透性的关键调节剂。然而,由于大多数体外模型无法重现正常肠道上皮中观察到的分化组织结构和成分,宿主-病原体相互作用的分子基础仍不清楚。最近的进展导致了一种源自肠上皮干细胞的新型细胞模型的发展,即类器官,它包含所有的上皮细胞类型,并复制了肠道组织的生理特性。本文总结了肠道屏障功能的分子方面以及肠道细菌-上皮细胞相互作用的参与。这篇综述还重点介绍了上皮类器官作为研究肠道微生物群-宿主相互作用分子方面的上皮屏障功能的有前途的模型。

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