Plasma Markers of Disrupted Gut Permeability in Severe COVID-19 Patients

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...

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Published in:Frontiers in immunology Vol. 12; p. 686240
Main Authors: Giron, Leila B., Dweep, Harsh, Yin, Xiangfan, Wang, Han, Damra, Mohammad, Goldman, Aaron R., Gorman, Nicole, Palmer, Clovis S., Tang, Hsin-Yao, Shaikh, Maliha W., Forsyth, Christopher B., Balk, Robert A., Zilberstein, Netanel F., Liu, Qin, Kossenkov, Andrew, Keshavarzian, Ali, Landay, Alan, Abdel-Mohsen, Mohamed
Format: Journal Article
Language:English
Published: Switzerland Frontiers Media S.A 09.06.2021
Subjects:
COVID-19
COVID-19 - immunology
Female
Gastrointestinal Microbiome - immunology
Glycomics
Haptoglobins - metabolism
Humans
Immunology
inflammation
Inflammation - immunology
Intestines - physiology
Lipidomics
Male
Metabolomics
microbial translocation
Middle Aged
Permeability
Protein Precursors - metabolism
SARS-CoV-2
SARS-CoV-2 - physiology
Tight Junctions - metabolism
zonulin
COVID-19
microbial translocation
SARS-CoV-2
zonulin
glycomics
inflammation
metabolomics
lipidomics
ISSN:1664-3224, 1664-3224
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Summary: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.
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Reviewed by: Michael Jay Corley, University of Hawaii, United States; Tengchuan Jin, University of Science and Technology of China, China
Edited by: Nicholas Funderburg, The Ohio State University, United States
This article was submitted to Viral Immunology, a section of the journal Frontiers in Immunology
ISSN:1664-3224
1664-3224
DOI:10.3389/fimmu.2021.686240