Alterations in Gut Microbiota of Patients With COVID-19 During Time of Hospitalization

Study information

Reviewed Marked as Reviewed by Chloe on 2021/08/11

study design

case-control

Citation

PMID PubMed identifier for scientific articles.

32442562

DOI Digital object identifier for electronic documents.

10.1053/j.gastro.2020.05.048

URI

Authors

Zuo T, Zhang F, Lui GCY, Yeoh YK, Li AYL, Zhan H, Wan Y, Chung ACK, Cheung CP, Chen N, Lai CKC, Chen Z, Tso EYK, Fung KSC, Chan V, Ling L, Joynt G, Hui DSC, Chan FKL, Chan PKS, Ng SC

Journal

Gastroenterology

Year

2020

Keywords:

Bacteria, Coronavirus, Fecal Nucleic Acid, Gut Microbiome

BACKGROUND & AIMS: Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects gastrointestinal tissues, little is known about the roles of gut commensal microbes in susceptibility to and severity of infection. We investigated changes in fecal microbiomes of patients with SARS-CoV-2 infection during hospitalization and associations with severity and fecal shedding of virus. METHODS: We performed shotgun metagenomic sequencing analyses of fecal samples from 15 patients with Coronavirus Disease 2019 (COVID-19) in Hong Kong, from February 5 through March 17, 2020. Fecal samples were collected 2 or 3 times per week from time of hospitalization until discharge; disease was categorized as mild (no radiographic evidence of pneumonia), moderate (pneumonia was present), severe (respiratory rate ≥30/min, or oxygen saturation ≤93% when breathing ambient air), or critical (respiratory failure requiring mechanical ventilation, shock, or organ failure requiring intensive care). We compared microbiome data with those from 6 subjects with community-acquired pneumonia and 15 healthy individuals (controls). We assessed gut microbiome profiles in association with disease severity and changes in fecal shedding of SARS-CoV-2. RESULTS: Patients with COVID-19 had significant alterations in fecal microbiomes compared with controls, characterized by enrichment of opportunistic pathogens and depletion of beneficial commensals, at time of hospitalization and at all timepoints during hospitalization. Depleted symbionts and gut dysbiosis persisted even after clearance of SARS-CoV-2 (determined from throat swabs) and resolution of respiratory symptoms. The baseline abundance of Coprobacillus, Clostridium ramosum, and Clostridium hathewayi correlated with COVID-19 severity; there was an inverse correlation between abundance of Faecalibacterium prausnitzii (an anti-inflammatory bacterium) and disease severity. Over the course of hospitalization, Bacteroides dorei, Bacteroides thetaiotaomicron, Bacteroides massiliensis, and Bacteroides ovatus, which downregulate expression of angiotensin-converting enzyme 2 (ACE2) in murine gut, correlated inversely with SARS-CoV-2 load in fecal samples from patients. CONCLUSIONS: In a pilot study of 15 patients with COVID-19, we found persistent alterations in the fecal microbiome during the time of hospitalization, compared with controls. Fecal microbiota alterations were associated with fecal levels of SARS-CoV-2 and COVID-19 severity. Strategies to alter the intestinal microbiota might reduce disease severity.

Experiment 1

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Reviewed Marked as Reviewed by Chloe on 2021/08/11

Curated date: 2021/07/02

Curator: Claregrieve1

Revision editor(s): WikiWorks, Chloe, Claregrieve1, Peace Sandy

Subjects

Location of subjects: China

Host species Species from which microbiome was sampled. Contact us to have more species added.: Homo sapiens

Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology: Feces Cow dung,Cow pat,Droppings,Dung,Excrement,Excreta,Faeces,Fecal material,Fecal matter,Fewmet,Frass,Guano,Matières fécales@fr,Merde@fr,Ordure,Partie de la merde@fr,Piece of shit,Porción de mierda@es,Portion of dung,Portion of excrement,Portion of faeces,Portion of fecal material,Portion of fecal matter,Portion of feces,Portion of guano,Portion of scat,Portionem cacas,Scat,Spoor,Spraint,Stool,Teil der fäkalien@de,Feces,feces

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology: COVID-19 2019 novel coronavirus,2019 novel coronavirus infection,2019-nCoV,2019-nCoV infection,beta-CoV,beta-CoVs,betacoronavirus,coronavirus disease 2019,SARS-coronavirus 2,SARS-CoV-2,severe acute respiratory syndrome coronavirus 2,severe acute respiratory syndrome coronavirus 2 infectious disease,β-coronavirus,β-CoV,β-CoVs,COVID-19,cOVID-19

Group 0 name Corresponds to the control (unexposed) group for case-control studies: Uninfected controls, pneumonia patients, antibiotics treated COVID-19 patients

Group 1 name Corresponds to the case (exposed) group for case-control studies: Antibiotic-naive COVID-19 patients

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: COVID-19 patients hospitalized with SARS-CoV-2 infection confirmed by 2 consecutive RT-PCR tests, not treated with antibiotics

Group 0 sample size Number of subjects in the control (unexposed) group: 29

Group 1 sample size Number of subjects in the case (exposed) group: 7

Lab analysis

Sequencing type: WMS

16S variable region One or more hypervariable region(s) of the bacterial 16S gene: Not specified

Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance: Illumina

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).: raw counts

Statistical test: Linear Regression

Significance threshold p-value or FDR threshold used for differential abundance testing (if any): 0.05

MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?: Yes

Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment: age, antibiotic exposure, comorbidity, sex

Signature 1

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Reviewed Marked as Reviewed by Chloe on 2021/08/11

Curated date: 2021/07/02

Curator: Claregrieve1

Revision editor(s): Claregrieve1

Source: Table 2

Description: Differential abundance of microbial taxa between antibiotic-naive COVID-19 patients and healthy controls

Abundance in Group 1: increased abundance in Antibiotic-naive COVID-19 patients

NCBI	Quality Control	Links
Actinomyces viscosus
Hungatella hathewayi CAG:224
Bacteroides nordii

Revision editor(s): Claregrieve1

Signature 2

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Reviewed Marked as Reviewed by Chloe on 2021/08/11

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Source: Table 2

Description: Differential abundance of microbial taxa between antibiotic-naive COVID-19 patients and healthy controls

Abundance in Group 1: decreased abundance in Antibiotic-naive COVID-19 patients

NCBI	Quality Control	Links
Eubacterium ventriosum

Revision editor(s): Chloe

Experiment 2

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Curated date: 2021/07/02

Curator: Claregrieve1

Revision editor(s): WikiWorks, Chloe, Claregrieve1, Victoria

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies: Antibiotic-naive COVID-19 patients, pneumonia patients, uninfected controls

Group 1 name Corresponds to the case (exposed) group for case-control studies: Antibiotic-treated COVID-19 patients

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: COVID-19 patients hospitalized with SARS-CoV-2 infection confirmed by 2 consecutive RT-PCR tests, treated with antibiotics

Group 0 sample size Number of subjects in the control (unexposed) group: 28

Group 1 sample size Number of subjects in the case (exposed) group: 8

Lab analysis

Statistical Analysis

Signature 1

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Reviewed Marked as Reviewed by Chloe on 2021/08/11

Curated date: 2021/07/02

Curator: Claregrieve1

Revision editor(s): Claregrieve1

Source: Table 2

Description: Differential abundance of microbial taxa between antibiotic-naive and antibiotic-treated COVID-19 patients

Abundance in Group 1: decreased abundance in Antibiotic-treated COVID-19 patients

NCBI	Quality Control	Links
Dorea formicigenerans
Blautia
Faecalibacterium
Faecalibacterium prausnitzii
Eubacteriaceae
Eubacterium
Agathobacter rectalis CAG:36
Oscillospiraceae
Roseburia
Coprococcus
Blautia obeum CAG:39
Lachnospiraceae bacterium 5_1_63FAA
Eubacterium ventriosum

Revision editor(s): Claregrieve1

Experiment 3

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Reviewed Marked as Reviewed by Chloe on 2021/08/11

Curated date: 2021/07/02

Curator: Claregrieve1

Revision editor(s): WikiWorks, Chloe, Claregrieve1, Victoria

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies: Uninfected controls, COVID-19 patients

Group 1 name Corresponds to the case (exposed) group for case-control studies: Pneumonia controls

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: Patients hospitalized with community-acquired pneumonia