Lost microbes of COVID-19: Bifidobacterium, Faecalibacterium depletion and decreased microbiome diversity associated with SARS-CoV-2 infection severity

Objective The study objective was to compare gut microbiome diversity and composition in SARS-CoV-2 PCR-positive patients whose symptoms ranged from asymptomatic to severe versus PCR-negative exposed controls.Design Using a cross-sectional design, we performed shotgun next-generation sequencing on s...

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Main Authors: Eamonn MM Quigley, Thomas J Borody, Sabine Hazan, Neil Stollman, Huseyin S Bozkurt, Sonya Dave, Andreas J Papoutsis, Jordan Daniels, Brad D Barrows
Format: Article
Language:English
Published: BMJ Publishing Group 2022-04-01
Series:BMJ Open Gastroenterology
Online Access:https://bmjopengastro.bmj.com/content/9/1/e000871.full
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author Eamonn MM Quigley
Thomas J Borody
Sabine Hazan
Neil Stollman
Huseyin S Bozkurt
Sonya Dave
Andreas J Papoutsis
Jordan Daniels
Brad D Barrows
author_facet Eamonn MM Quigley
Thomas J Borody
Sabine Hazan
Neil Stollman
Huseyin S Bozkurt
Sonya Dave
Andreas J Papoutsis
Jordan Daniels
Brad D Barrows
author_sort Eamonn MM Quigley
collection DOAJ
description Objective The study objective was to compare gut microbiome diversity and composition in SARS-CoV-2 PCR-positive patients whose symptoms ranged from asymptomatic to severe versus PCR-negative exposed controls.Design Using a cross-sectional design, we performed shotgun next-generation sequencing on stool samples to evaluate gut microbiome composition and diversity in both patients with SARS-CoV-2 PCR-confirmed infections, which had presented to Ventura Clinical Trials for care from March 2020 through October 2021 and SARS-CoV-2 PCR-negative exposed controls. Patients were classified as being asymptomatic or having mild, moderate or severe symptoms based on National Institute of Health criteria. Exposed controls were individuals with prolonged or repeated close contact with patients with SARS-CoV-2 infection or their samples, for example, household members of patients or frontline healthcare workers. Microbiome diversity and composition were compared between patients and exposed controls at all taxonomic levels.Results Compared with controls (n=20), severely symptomatic SARS-CoV-2-infected patients (n=28) had significantly less bacterial diversity (Shannon Index, p=0.0499; Simpson Index, p=0.0581), and positive patients overall had lower relative abundances of Bifidobacterium (p<0.0001), Faecalibacterium (p=0.0077) and Roseburium (p=0.0327), while having increased Bacteroides (p=0.0075). Interestingly, there was an inverse association between disease severity and abundance of the same bacteria.Conclusion We hypothesise that low bacterial diversity and depletion of Bifidobacterium genera either before or after infection led to reduced proimmune function, thereby allowing SARS-CoV-2 infection to become symptomatic. This particular dysbiosis pattern may be a susceptibility marker for symptomatic severity from SARS-CoV-2 infection and may be amenable to preinfection, intrainfection or postinfection intervention.Trial registration number NCT04031469 (PCR−) and 04359836 (PCR+).
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spelling doaj-art-4f2ed47536cd4ecdb984fbb4acdd41b62025-02-07T16:55:09ZengBMJ Publishing GroupBMJ Open Gastroenterology2054-47742022-04-019110.1136/bmjgast-2022-000871Lost microbes of COVID-19: Bifidobacterium, Faecalibacterium depletion and decreased microbiome diversity associated with SARS-CoV-2 infection severityEamonn MM Quigley0Thomas J Borody1Sabine Hazan2Neil Stollman3Huseyin S Bozkurt4Sonya Dave5Andreas J Papoutsis6Jordan Daniels7Brad D Barrows8Division of Gastroenterology and Hepatology, The Methodist Hospital, Weill Cornell Medical College, Houston, Texas, USACentre for Digestive Diseases, Sydney, New South Wales, AustraliaN/A, ProgenaBiome LLC, Ventura, California, USADivision of Gastroenterology, Alta Bates Summit Medical Center, Berkeley, California, USAClinic of Gastroenterology, Istanbul Maltepe University, Istanbul, TurkeyN/A, Microbiome Research, Inc, Ventura, California, USAN/A, ProgenaBiome LLC, Ventura, California, USAN/A, ProgenaBiome LLC, Ventura, California, USAN/A, ProgenaBiome LLC, Ventura, California, USAObjective The study objective was to compare gut microbiome diversity and composition in SARS-CoV-2 PCR-positive patients whose symptoms ranged from asymptomatic to severe versus PCR-negative exposed controls.Design Using a cross-sectional design, we performed shotgun next-generation sequencing on stool samples to evaluate gut microbiome composition and diversity in both patients with SARS-CoV-2 PCR-confirmed infections, which had presented to Ventura Clinical Trials for care from March 2020 through October 2021 and SARS-CoV-2 PCR-negative exposed controls. Patients were classified as being asymptomatic or having mild, moderate or severe symptoms based on National Institute of Health criteria. Exposed controls were individuals with prolonged or repeated close contact with patients with SARS-CoV-2 infection or their samples, for example, household members of patients or frontline healthcare workers. Microbiome diversity and composition were compared between patients and exposed controls at all taxonomic levels.Results Compared with controls (n=20), severely symptomatic SARS-CoV-2-infected patients (n=28) had significantly less bacterial diversity (Shannon Index, p=0.0499; Simpson Index, p=0.0581), and positive patients overall had lower relative abundances of Bifidobacterium (p<0.0001), Faecalibacterium (p=0.0077) and Roseburium (p=0.0327), while having increased Bacteroides (p=0.0075). Interestingly, there was an inverse association between disease severity and abundance of the same bacteria.Conclusion We hypothesise that low bacterial diversity and depletion of Bifidobacterium genera either before or after infection led to reduced proimmune function, thereby allowing SARS-CoV-2 infection to become symptomatic. This particular dysbiosis pattern may be a susceptibility marker for symptomatic severity from SARS-CoV-2 infection and may be amenable to preinfection, intrainfection or postinfection intervention.Trial registration number NCT04031469 (PCR−) and 04359836 (PCR+).https://bmjopengastro.bmj.com/content/9/1/e000871.full
spellingShingle Eamonn MM Quigley
Thomas J Borody
Sabine Hazan
Neil Stollman
Huseyin S Bozkurt
Sonya Dave
Andreas J Papoutsis
Jordan Daniels
Brad D Barrows
Lost microbes of COVID-19: Bifidobacterium, Faecalibacterium depletion and decreased microbiome diversity associated with SARS-CoV-2 infection severity
BMJ Open Gastroenterology
title Lost microbes of COVID-19: Bifidobacterium, Faecalibacterium depletion and decreased microbiome diversity associated with SARS-CoV-2 infection severity
title_full Lost microbes of COVID-19: Bifidobacterium, Faecalibacterium depletion and decreased microbiome diversity associated with SARS-CoV-2 infection severity
title_fullStr Lost microbes of COVID-19: Bifidobacterium, Faecalibacterium depletion and decreased microbiome diversity associated with SARS-CoV-2 infection severity
title_full_unstemmed Lost microbes of COVID-19: Bifidobacterium, Faecalibacterium depletion and decreased microbiome diversity associated with SARS-CoV-2 infection severity
title_short Lost microbes of COVID-19: Bifidobacterium, Faecalibacterium depletion and decreased microbiome diversity associated with SARS-CoV-2 infection severity
title_sort lost microbes of covid 19 bifidobacterium faecalibacterium depletion and decreased microbiome diversity associated with sars cov 2 infection severity
url https://bmjopengastro.bmj.com/content/9/1/e000871.full
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