A disruption of the crosstalk between the gut and the lung has been implicated as a driver of severity during respiratory-related diseases. Lung injury causes systemic inflammation, which disrupts gut barrier integrity, increasing the permeability to gut microbes and their products. This exacerbates inflammation, resulting in positive feedback. We aimed to test whether severe Coronavirus disease 2019 (COVID-19) is associated with markers of disrupted gut permeability. We applied a multi-omic systems biology approach to analyze plasma samples from COVID-19 patients with varying disease severity and SARS-CoV-2 negative controls. We investigated the potential links between plasma markers of gut barrier integrity, microbial translocation, systemic inflammation, metabolome, lipidome, and glycome, and COVID-19 severity. We found that severe COVID-19 is associated with high levels of markers of tight junction permeability and translocation of bacterial and fungal products into the blood. These markers of disrupted intestinal barrier integrity and microbial translocation correlate strongly with higher levels of markers of systemic inflammation and immune activation, lower levels of markers of intestinal function, disrupted plasma metabolome and glycome, and higher mortality rate. Our study highlights an underappreciated factor with significant clinical implications, disruption in gut functions, as a potential force that may contribute to COVID-19 severity.
【저자키워드】 COVID-19, SARS-CoV-2, Inflammation, metabolomics, Lipidomics, microbial translocation, zonulin, glycomics, 【초록키워드】 coronavirus disease, Coronavirus disease 2019, Crosstalk, Diseases, severe COVID-19, severity, disease severity, COVID-19 severity, lung, metabolome, Systems biology, Lung injury, immune activation, positive feedback, systemic inflammation, mortality rate, fungal, COVID-19 patients, Blood, Bacterial, Plasma marker, marker, tight junction, microbe, permeability, Injury, COVID-19 patient, Disruption, Gut, microbial, severe coronavirus disease, plasma metabolome, negative controls, plasma samples, functions, positive, microbes, translocation, clinical implications, glycome, gut barrier integrity, approach, intestinal, plasma markers, highlight, plasma sample, resulting, investigated, applied, contribute, cause, implicated, disrupt, exacerbate, 【제목키워드】 Disrupted,