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 ...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 dysregu-lation 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.展开更多
文摘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 dysregu-lation 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.
