TY - JOUR
T1 - Lost microbes of COVID-19
T2 - Bifidobacterium, Faecalibacterium depletion and decreased microbiome diversity associated with SARS-CoV-2 infection severity
AU - Hazan, Sabine
AU - Stollman, Neil
AU - Bozkurt, Huseyin S.
AU - Dave, Sonya
AU - Papoutsis, Andreas J.
AU - Daniels, Jordan
AU - Barrows, Brad D.
AU - Quigley, Eamonn M.M.
AU - Borody, Thomas J.
N1 - Funding Information:
1N/A, ProgenaBiome LLC, Ventura, California, USA 2Division of Gastroenterology, Alta Bates Summit Medical Center, Berkeley, California, USA 3Clinic of Gastroenterology, Istanbul Maltepe University, Istanbul, Turkey 4N/A, Microbiome Research, Inc, Ventura, California, USA 5Medical Writing and Biostatistics, North End Advisory, Smyrna, Georgia, USA 6Division of Gastroenterology and Hepatology, The Methodist Hospital, Weill Cornell Medical College, Houston, Texas, USA 7N/A, Centre for Digestive Diseases, Five Dock, New South Wales, Australia Acknowledgements Medical writing assistance was provided by Sonya Dave, PhD (an author on the publication) and was funded by ProgenaBiome. The authors thank all clinicians for their involvement and contribution to the study. The authors thank Kate Hendricks, MD, MPH and TM for many helpful editorial suggestions. Finally, the authors owe a depth of gratitude to the late Sydney M Finegold, MD for mentorship that sparked the interest in the microbiome to many scientists, including authors of this paper.
Publisher Copyright:
© Author(s) (or their employer(s)) 2022.
© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
PY - 2022/4/28
Y1 - 2022/4/28
N2 - 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+).
AB - 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+).
KW - BACTERIAL INFECTION
KW - BIFIDOBACTERIA
KW - ENTERIC BACTERIAL MICROFLORA
KW - INTESTINAL MICROBIOLOGY
KW - COVID-19
KW - Microbiota
KW - SARS-CoV-2
KW - Cross-Sectional Studies
KW - Humans
KW - Bifidobacterium/genetics
KW - Faecalibacterium
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U2 - 10.1136/bmjgast-2022-000871
DO - 10.1136/bmjgast-2022-000871
M3 - Article
C2 - 35483736
AN - SCOPUS:85130967943
SN - 2054-4774
VL - 9
JO - BMJ Open Gastroenterology
JF - BMJ Open Gastroenterology
IS - 1
M1 - e000871
ER -