Plasma Microbiome in COVID-19 Subjects: An Indicator of Gut Barrier Defects and Dysbiosis

The gut is a well-established route of infection and target for viral damage by SARS-CoV-2. This is supported by the clinical observation that about half of COVID-19 patients exhibit gastrointestinal (GI) complications. We aimed to investigate whether the analysis of plasma could provide insight int...

Full description

Bibliographic Details
Main Authors: Ram Prasad, Michael John Patton, Jason Levi. Floyd, Seth Fortmann, Mariana DuPont, Angela Harbour, Justin Wright, Regina Lamendella, Bruce R. Stevens, Gavin Y. Oudit, Maria B. Grant
Format: Article
Language:English
Published: MDPI AG 2022-08-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/23/16/9141
_version_ 1797444769675214848
author Ram Prasad
Michael John Patton
Jason Levi. Floyd
Seth Fortmann
Mariana DuPont
Angela Harbour
Justin Wright
Regina Lamendella
Bruce R. Stevens
Gavin Y. Oudit
Maria B. Grant
author_facet Ram Prasad
Michael John Patton
Jason Levi. Floyd
Seth Fortmann
Mariana DuPont
Angela Harbour
Justin Wright
Regina Lamendella
Bruce R. Stevens
Gavin Y. Oudit
Maria B. Grant
author_sort Ram Prasad
collection DOAJ
description The gut is a well-established route of infection and target for viral damage by SARS-CoV-2. This is supported by the clinical observation that about half of COVID-19 patients exhibit gastrointestinal (GI) complications. We aimed to investigate whether the analysis of plasma could provide insight into gut barrier dysfunction in patients with COVID-19 infection. Plasma samples of COVID-19 patients (<i>n</i> = 146) and healthy individuals (<i>n</i> = 47) were collected during hospitalization and routine visits. Plasma microbiome was analyzed using 16S rRNA sequencing and gut permeability markers including fatty acid binding protein 2 (FABP2), peptidoglycan (PGN), and lipopolysaccharide (LPS) in both patient cohorts. Plasma samples of both cohorts contained predominately <i>Proteobacteria</i>, <i>Firmicutes</i>, <i>Bacteroides</i>, and <i>Actinobacteria</i>. COVID-19 subjects exhibit significant dysbiosis (<i>p</i> = 0.001) of the plasma microbiome with increased abundance of <i>Actinobacteria</i> spp. (<i>p</i> = 0.0332), decreased abundance of <i>Bacteroides</i> spp. (<i>p</i> = 0.0003), and an increased <i>Firmicutes:Bacteroidetes</i> ratio (<i>p</i> = 0.0003) compared to healthy subjects. The concentration of the plasma gut permeability marker FABP2 (<i>p</i> = 0.0013) and the gut microbial antigens PGN (<i>p</i> < 0.0001) and LPS (<i>p</i> = 0.0049) were significantly elevated in COVID-19 patients compared to healthy subjects. These findings support the notion that the intestine may represent a source for bacteremia and contribute to worsening COVID-19 outcomes. Therapies targeting the gut and prevention of gut barrier defects may represent a strategy to improve outcomes in COVID-19 patients.
first_indexed 2024-03-09T13:17:21Z
format Article
id doaj.art-4f295dcf39a3462191f358ab061d48e9
institution Directory Open Access Journal
issn 1661-6596
1422-0067
language English
last_indexed 2024-03-09T13:17:21Z
publishDate 2022-08-01
publisher MDPI AG
record_format Article
series International Journal of Molecular Sciences
spelling doaj.art-4f295dcf39a3462191f358ab061d48e92023-11-30T21:34:31ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-08-012316914110.3390/ijms23169141Plasma Microbiome in COVID-19 Subjects: An Indicator of Gut Barrier Defects and DysbiosisRam Prasad0Michael John Patton1Jason Levi. Floyd2Seth Fortmann3Mariana DuPont4Angela Harbour5Justin Wright6Regina Lamendella7Bruce R. Stevens8Gavin Y. Oudit9Maria B. Grant10Department of Ophthalmology and Visual Sciences, University of Alabama at Birmingham, 1670 University BLVD, VH490, Birmingham, AL 35294, USAHugh Kaul Precision Medicine Institute, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USADepartment of Ophthalmology and Visual Sciences, University of Alabama at Birmingham, 1670 University BLVD, VH490, Birmingham, AL 35294, USADepartment of Ophthalmology and Visual Sciences, University of Alabama at Birmingham, 1670 University BLVD, VH490, Birmingham, AL 35294, USADepartment of Ophthalmology and Visual Sciences, University of Alabama at Birmingham, 1670 University BLVD, VH490, Birmingham, AL 35294, USADepartment of Ophthalmology and Visual Sciences, University of Alabama at Birmingham, 1670 University BLVD, VH490, Birmingham, AL 35294, USAWright Labs, LLC, Huntingdon, PA 16652, USAWright Labs, LLC, Huntingdon, PA 16652, USADepartment of Physiology and Functional Genomics, University of Florida, Gainesville, FL 32611, USADivision of Cardiology, Department of Medicine, University of Alberta, Mazankowski Alberta Heart Institute, Edmonton, AB T6G 2B7, CanadaDepartment of Ophthalmology and Visual Sciences, University of Alabama at Birmingham, 1670 University BLVD, VH490, Birmingham, AL 35294, USAThe gut is a well-established route of infection and target for viral damage by SARS-CoV-2. This is supported by the clinical observation that about half of COVID-19 patients exhibit gastrointestinal (GI) complications. We aimed to investigate whether the analysis of plasma could provide insight into gut barrier dysfunction in patients with COVID-19 infection. Plasma samples of COVID-19 patients (<i>n</i> = 146) and healthy individuals (<i>n</i> = 47) were collected during hospitalization and routine visits. Plasma microbiome was analyzed using 16S rRNA sequencing and gut permeability markers including fatty acid binding protein 2 (FABP2), peptidoglycan (PGN), and lipopolysaccharide (LPS) in both patient cohorts. Plasma samples of both cohorts contained predominately <i>Proteobacteria</i>, <i>Firmicutes</i>, <i>Bacteroides</i>, and <i>Actinobacteria</i>. COVID-19 subjects exhibit significant dysbiosis (<i>p</i> = 0.001) of the plasma microbiome with increased abundance of <i>Actinobacteria</i> spp. (<i>p</i> = 0.0332), decreased abundance of <i>Bacteroides</i> spp. (<i>p</i> = 0.0003), and an increased <i>Firmicutes:Bacteroidetes</i> ratio (<i>p</i> = 0.0003) compared to healthy subjects. The concentration of the plasma gut permeability marker FABP2 (<i>p</i> = 0.0013) and the gut microbial antigens PGN (<i>p</i> < 0.0001) and LPS (<i>p</i> = 0.0049) were significantly elevated in COVID-19 patients compared to healthy subjects. These findings support the notion that the intestine may represent a source for bacteremia and contribute to worsening COVID-19 outcomes. Therapies targeting the gut and prevention of gut barrier defects may represent a strategy to improve outcomes in COVID-19 patients.https://www.mdpi.com/1422-0067/23/16/9141circulating microbiomeCOVID-19gut barrier permeabilitydysbiosis
spellingShingle Ram Prasad
Michael John Patton
Jason Levi. Floyd
Seth Fortmann
Mariana DuPont
Angela Harbour
Justin Wright
Regina Lamendella
Bruce R. Stevens
Gavin Y. Oudit
Maria B. Grant
Plasma Microbiome in COVID-19 Subjects: An Indicator of Gut Barrier Defects and Dysbiosis
International Journal of Molecular Sciences
circulating microbiome
COVID-19
gut barrier permeability
dysbiosis
title Plasma Microbiome in COVID-19 Subjects: An Indicator of Gut Barrier Defects and Dysbiosis
title_full Plasma Microbiome in COVID-19 Subjects: An Indicator of Gut Barrier Defects and Dysbiosis
title_fullStr Plasma Microbiome in COVID-19 Subjects: An Indicator of Gut Barrier Defects and Dysbiosis
title_full_unstemmed Plasma Microbiome in COVID-19 Subjects: An Indicator of Gut Barrier Defects and Dysbiosis
title_short Plasma Microbiome in COVID-19 Subjects: An Indicator of Gut Barrier Defects and Dysbiosis
title_sort plasma microbiome in covid 19 subjects an indicator of gut barrier defects and dysbiosis
topic circulating microbiome
COVID-19
gut barrier permeability
dysbiosis
url https://www.mdpi.com/1422-0067/23/16/9141
work_keys_str_mv AT ramprasad plasmamicrobiomeincovid19subjectsanindicatorofgutbarrierdefectsanddysbiosis
AT michaeljohnpatton plasmamicrobiomeincovid19subjectsanindicatorofgutbarrierdefectsanddysbiosis
AT jasonlevifloyd plasmamicrobiomeincovid19subjectsanindicatorofgutbarrierdefectsanddysbiosis
AT sethfortmann plasmamicrobiomeincovid19subjectsanindicatorofgutbarrierdefectsanddysbiosis
AT marianadupont plasmamicrobiomeincovid19subjectsanindicatorofgutbarrierdefectsanddysbiosis
AT angelaharbour plasmamicrobiomeincovid19subjectsanindicatorofgutbarrierdefectsanddysbiosis
AT justinwright plasmamicrobiomeincovid19subjectsanindicatorofgutbarrierdefectsanddysbiosis
AT reginalamendella plasmamicrobiomeincovid19subjectsanindicatorofgutbarrierdefectsanddysbiosis
AT brucerstevens plasmamicrobiomeincovid19subjectsanindicatorofgutbarrierdefectsanddysbiosis
AT gavinyoudit plasmamicrobiomeincovid19subjectsanindicatorofgutbarrierdefectsanddysbiosis
AT mariabgrant plasmamicrobiomeincovid19subjectsanindicatorofgutbarrierdefectsanddysbiosis