Intestinal barrier dysfunction as a key driver of severe COVID-19.

Efthymios P Tsounis, Christos Triantos, Christos Konstantakis, Markos Marangos, Stelios F Assimakopoulos
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引用次数: 2

Abstract

The intestinal lumen harbors a diverse consortium of microorganisms that participate in reciprocal crosstalk with intestinal immune cells and with epithelial and endothelial cells, forming a multi-layered barrier that enables the efficient absorption of nutrients without an excessive influx of pathogens. Despite being a lung-centered disease, severe coronavirus disease 2019 (COVID-19) affects multiple systems, including the gastrointestinal tract and the pertinent gut barrier function. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can inflict either direct cytopathic injury to intestinal epithelial and endothelial cells or indirect immune-mediated damage. Alternatively, SARS-CoV-2 undermines the structural integrity of the barrier by modifying the expression of tight junction proteins. In addition, SARS-CoV-2 induces profound alterations to the intestinal microflora at phylogenetic and metabolomic levels (dysbiosis) that are accompanied by disruption of local immune responses. The ensuing dysregulation of the gut-lung axis impairs the ability of the respiratory immune system to elicit robust and timely responses to restrict viral infection. The intestinal vasculature is vulnerable to SARS-CoV-2-induced endothelial injury, which simultaneously triggers the activation of the innate immune and coagulation systems, a condition referred to as "immunothrombosis" that drives severe thrombotic complications. Finally, increased intestinal permeability allows an aberrant dissemination of bacteria, fungi, and endotoxin into the systemic circulation and contributes, to a certain degree, to the over-exuberant immune responses and hyper-inflammation that dictate the severe form of COVID-19. In this review, we aim to elucidate SARS-CoV-2-mediated effects on gut barrier homeostasis and their implications on the progression of the disease.

Abstract Image

Abstract Image

肠道屏障功能障碍是严重COVID-19的关键驱动因素。
肠道内容纳着多种微生物,它们与肠道免疫细胞、上皮细胞和内皮细胞相互作用,形成多层屏障,使营养物质能够有效吸收,而不会过量涌入病原体。尽管是一种以肺部为中心的疾病,但2019年严重冠状病毒病(COVID-19)会影响多个系统,包括胃肠道和相关的肠道屏障功能。严重急性呼吸综合征冠状病毒2 (SARS-CoV-2)可对肠上皮细胞和内皮细胞造成直接的细胞病变损伤或间接免疫介导的损伤。或者,SARS-CoV-2通过改变紧密连接蛋白的表达来破坏屏障的结构完整性。此外,SARS-CoV-2在系统发育和代谢组学水平上诱发肠道微生物群的深刻改变(生态失调),并伴有局部免疫反应的破坏。随后的肠-肺轴的失调损害了呼吸免疫系统的能力,从而引发强大和及时的反应来限制病毒感染。肠道血管很容易受到sars - cov -2诱导的内皮损伤的影响,这同时会触发先天免疫和凝血系统的激活,这种情况被称为“免疫血栓形成”,会导致严重的血栓并发症。最后,肠道通透性增加导致细菌、真菌和内毒素进入体循环,并在一定程度上导致过度活跃的免疫反应和过度炎症,从而导致COVID-19的严重形式。在这篇综述中,我们旨在阐明sars - cov -2介导的对肠道屏障稳态的影响及其对疾病进展的影响。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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