Reversion of Gut Microbiota during the Recovery Phase in Patients with Asymptomatic or Mild COVID-19: Longitudinal Study

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Needs review
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI Uniform resource identifier for web resources.
Authors
Kim HN, Joo EJ, Lee CW, Ahn KS, Kim HL, Park DI, Park SK
Journal
Microorganisms
Year
2021
Patients with COVID-19 have been reported to experience gastrointestinal symptoms as well as respiratory symptoms, but the effects of COVID-19 on the gut microbiota are poorly understood. We explored gut microbiome profiles associated with the respiratory infection of SARS-CoV-2 during the recovery phase in patients with asymptomatic or mild COVID-19. A longitudinal analysis was performed using the same patients to determine whether the gut microbiota changed after recovery from COVID-19. We applied 16S rRNA amplicon sequencing to analyze two paired fecal samples from 12 patients with asymptomatic or mild COVID-19. Fecal samples were selected at two time points: during SARS-CoV-2 infection (infected state) and after negative conversion of the viral RNA (recovered state). We also compared the microbiome data with those from 36 healthy controls. Microbial evenness of the recovered state was significantly increased compared with the infected state. SARS-CoV-2 infection induced the depletion of Bacteroidetes, while an abundance was observed with a tendency to rapidly reverse in the recovered state. The Firmicutes/Bacteroidetes ratio in the infected state was markedly higher than that in the recovered state. Gut dysbiosis was observed after infection even in patients with asymptomatic or mild COVID-19, while the composition of the gut microbiota was recovered after negative conversion of SARS-CoV-2 RNA. Modifying intestinal microbes in response to COVID-19 might be a useful therapeutic alternative.

Experiment 1


Needs review

Curated date: 2021/07/04

Curator: Claregrieve1

Revision editor(s): Claregrieve1, WikiWorks

Subjects

Location of subjects
South Korea
Host species Species from which microbiome was sampled (if applicable)
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
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
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Infected COVID-19 samples (respiratory positive)
Group 1 name Corresponds to the case (exposed) group for case-control studies
Recovered COVID-19 samples (respiratory negative)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Samples from symptomatic/mild COVID-19 patients collected on or after negative conversion for SARS-CoV-2 RNA from the respiratory tract
Group 0 sample size Number of subjects in the control (unexposed) group
12
Group 1 sample size Number of subjects in the case (exposed) group
12
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
No history of antibiotics or probiotics

Lab analysis

Sequencing type
16S
16S variable region One or more hypervariable region(s) of the bacterial 16S gene
V3-V4
Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
Illumina

Statistical Analysis

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


Alpha Diversity

Pielou Quantifies how equal the community is numerically
increased
Shannon Estimator of species richness and species evenness: more weight on species richness
unchanged
Richness Number of species
unchanged

Signature 1

Needs review

Curated date: 2021/07/04

Curator: Claregrieve1

Revision editor(s): Claregrieve1

Source: Supplementary Table S1

Description: Comparison of taxonomic compositions of gut microbiota between respiratory positive and respiratory negative COVID-19 samples

Abundance in Group 1: increased abundance in Recovered COVID-19 samples (respiratory negative)

NCBI Links
Bacteroidota
Bacteroidia
Bacteroidales

Revision editor(s): Claregrieve1

Signature 2

Needs review

Curated date: 2021/07/04

Curator: Claregrieve1

Revision editor(s): Claregrieve1

Source: Supplementary Table S1

Description: Comparison of taxonomic compositions of gut microbiota between respiratory positive and respiratory negative COVID-19 samples

Abundance in Group 1: decreased abundance in Recovered COVID-19 samples (respiratory negative)

NCBI Links
Actinomycetales

Revision editor(s): Claregrieve1

Experiment 2


Needs review

Curated date: 2021/07/04

Curator: Claregrieve1

Revision editor(s): Claregrieve1, WikiWorks

Subjects

Location of subjects
South Korea
Host species Species from which microbiome was sampled (if applicable)
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
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
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Healthy controls
Group 1 name Corresponds to the case (exposed) group for case-control studies
Recovered COVID-19 samples (respiratory negative)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Samples from symptomatic/mild COVID-19 patients collected on or after negative conversion for SARS-CoV-2 RNA from the respiratory tract
Group 0 sample size Number of subjects in the control (unexposed) group
36
Group 1 sample size Number of subjects in the case (exposed) group
12
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
No history of antibiotics or probiotics

Lab analysis

Sequencing type
16S
Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
Illumina

Statistical Analysis

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


Alpha Diversity

Pielou Quantifies how equal the community is numerically
decreased
Shannon Estimator of species richness and species evenness: more weight on species richness
unchanged
Richness Number of species
increased

Signature 1

Needs review

Curated date: 2021/07/04

Curator: Claregrieve1

Revision editor(s): Claregrieve1

Source: Supplementary Table S2

Description: Comparison of taxonomic composition of gut microbiota in respiratory-negative recovered COVID-19 patients and healthy controls

Abundance in Group 1: decreased abundance in Recovered COVID-19 samples (respiratory negative)

NCBI Links
Negativicutes
Selenomonadales
monoglobalesmonoglobales
Oscillospiraceae
monoglobaceaemonoglobaceae
oscillospiraceae UCG 002oscillospiraceae UCG 002
oscillospiraceae UCG 003oscillospiraceae UCG 003
Lachnospiraceae bacterium NK4A136
rumen bacterium NK4A214
Roseburia
Anaerostipes
Monoglobus
Fusicatenibacter
Family XIII UCG 001Family XIII UCG 001
Coprococcus
UCG 005UCG 005

Revision editor(s): Claregrieve1

Signature 2

Needs review

Curated date: 2021/07/04

Curator: Claregrieve1

Revision editor(s): Claregrieve1

Source: Supplementary Table S2

Description: Comparison of taxonomic composition of gut microbiota in respiratory-negative recovered COVID-19 patients and healthy controls

Abundance in Group 1: increased abundance in Recovered COVID-19 samples (respiratory negative)

NCBI Links
Actinomycetota
Pseudomonadota
Coriobacteriia
Bacilli
Gammaproteobacteria
Coriobacteriales
Lactobacillales
Enterobacterales
Coriobacteriaceae
Enterococcaceae
Lactobacillaceae
Eggerthellaceae
Streptococcaceae
Peptostreptococcaceae
Bifidobacteriaceae
Enterobacteriaceae
Clostridiaceae
Collinsella
Enterococcus
Lactobacillus
Streptococcus
Romboutsia
Faecalibacterium sp. UBA1819
Pediococcus
Citrobacter

Revision editor(s): Claregrieve1

Experiment 3


Needs review

Curated date: 2021/07/04

Curator: Claregrieve1

Revision editor(s): Claregrieve1, WikiWorks

Subjects

Location of subjects
South Korea
Host species Species from which microbiome was sampled (if applicable)
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
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
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Healthy controls
Group 1 name Corresponds to the case (exposed) group for case-control studies
Infected COVID-19 samples (respiratory positive)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Samples from symptomatic/mild COVID-19 patients collected on or before positive detection of SARS-CoV-2 RNA from the respiratory tract
Group 0 sample size Number of subjects in the control (unexposed) group
36
Group 1 sample size Number of subjects in the case (exposed) group
12
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
No history of antibiotics or probiotics

Lab analysis

Sequencing type
16S
Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
Illumina

Statistical Analysis

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


Alpha Diversity

Pielou Quantifies how equal the community is numerically
decreased
Shannon Estimator of species richness and species evenness: more weight on species richness
decreased
Richness Number of species
unchanged

Signature 1

Needs review

Curated date: 2021/07/04

Curator: Claregrieve1

Revision editor(s): Claregrieve1

Source: Supplementary Table S2

Description: Comparison of taxonomic composition of gut microbiota in respiratory-positive infected COVID-19 patients and healthy controls

Abundance in Group 1: decreased abundance in Infected COVID-19 samples (respiratory positive)

NCBI Links
Bacteroidota
Bacteroidia
Negativicutes
Bacteroidales
oscillospiralesoscillospirales
Selenomonadales
monoglobalesmonoglobales
Oscillospiraceae
Bacteroidaceae
Tannerellaceae
Marinifilaceae
Prevotellaceae
Rikenellaceae
butyricicoccaceaebutyricicoccaceae
monoglobaceaemonoglobaceae
Barnesiellaceae
Veillonellaceae
Eubacterium coprostanoligenes
Bacteroides
UCG 002UCG 002
Faecalibacterium
Parabacteroides
UCG 003UCG 003
Lachnospiraceae bacterium NK4A136
Sutterella
rumen bacterium NK4A214
Alistipes
Odoribacter
Roseburia
Anaerostipes
Ruminococcus
Lachnoclostridium
Agathobacter
Lachnospira
Butyricicoccus
Monoglobus
Colidextribacter
Paraprevotella
UCG 010UCG 010
Butyricimonas
Family XIII UCG 001Family XIII UCG 001
Prevotella
Oscillibacter
Lachnospira eligens
Coprococcus
UCG 005UCG 005
uncultured Oscillospira sp.
christensenellaceae R7christensenellaceae R7
Barnesiella

Revision editor(s): Claregrieve1

Signature 2

Needs review

Curated date: 2021/07/04

Curator: Claregrieve1

Revision editor(s): Claregrieve1

Source: Supplementary Table S2

Description: Comparison of taxonomic composition of gut microbiota in respiratory-positive infected COVID-19 patients and healthy controls

Abundance in Group 1: increased abundance in Infected COVID-19 samples (respiratory positive)

NCBI Links
Actinomycetota
Pseudomonadota
Coriobacteriia
Bacilli
Gammaproteobacteria
Coriobacteriales
Lactobacillales
Tissierellales
Bifidobacteriales
Enterobacterales
Eubacteriales
Coriobacteriaceae
Enterococcaceae
Lactobacillaceae
Eggerthellaceae
Streptococcaceae
Peptostreptococcaceae
Bifidobacteriaceae
Enterobacteriaceae
Clostridiaceae
Collinsella
Enterococcus
Lactobacillus
Streptococcus
Turicibacter
Romboutsia
Pediococcus
Blautia
Anaerobutyricum hallii
Shigella
Bifidobacterium
Clostridium
Intestinibacter

Revision editor(s): Claregrieve1