Gut microbiota composition reflects disease severity and dysfunctional immune responses in patients with COVID-19

From BugSigDB
Reviewed Marked as Reviewed by Fatima on 2021/09/16
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI Uniform resource identifier for web resources.
Authors
Yeoh YK, Zuo T, Lui GC, Zhang F, Liu Q, Li AY, Chung AC, Cheung CP, Tso EY, Fung KS, Chan V, Ling L, Joynt G, Hui DS, Chow KM, Ng SSS, Li TC, Ng RW, Yip TC, Wong GL, Chan FK, Wong CK, Chan PK, Ng SC
Journal
Gut
Year
2021
OBJECTIVE: Although COVID-19 is primarily a respiratory illness, there is mounting evidence suggesting that the GI tract is involved in this disease. We investigated whether the gut microbiome is linked to disease severity in patients with COVID-19, and whether perturbations in microbiome composition, if any, resolve with clearance of the SARS-CoV-2 virus. METHODS: In this two-hospital cohort study, we obtained blood, stool and patient records from 100 patients with laboratory-confirmed SARS-CoV-2 infection. Serial stool samples were collected from 27 of the 100 patients up to 30 days after clearance of SARS-CoV-2. Gut microbiome compositions were characterised by shotgun sequencing total DNA extracted from stools. Concentrations of inflammatory cytokines and blood markers were measured from plasma. RESULTS: Gut microbiome composition was significantly altered in patients with COVID-19 compared with non-COVID-19 individuals irrespective of whether patients had received medication (p<0.01). Several gut commensals with known immunomodulatory potential such as Faecalibacterium prausnitzii, Eubacterium rectale and bifidobacteria were underrepresented in patients and remained low in samples collected up to 30 days after disease resolution. Moreover, this perturbed composition exhibited stratification with disease severity concordant with elevated concentrations of inflammatory cytokines and blood markers such as C reactive protein, lactate dehydrogenase, aspartate aminotransferase and gamma-glutamyl transferase. CONCLUSION: Associations between gut microbiota composition, levels of cytokines and inflammatory markers in patients with COVID-19 suggest that the gut microbiome is involved in the magnitude of COVID-19 severity possibly via modulating host immune responses. Furthermore, the gut microbiota dysbiosis after disease resolution could contribute to persistent symptoms, highlighting a need to understand how gut microorganisms are involved in inflammation and COVID-19.

Experiment 1


Reviewed Marked as Reviewed by Fatima on 2021/09/16

Curated date: 2021/05/25

Curator: Claregrieve1

Revision editor(s): Claregrieve1, WikiWorks

Subjects

Location of subjects
China
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
COVID-19 cases
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Laboratory-confirmed SARS-CoV-2 positive by quantitative reverse transcription PCR performed on nasopharyngeal swabs
Group 0 sample size Number of subjects in the control (unexposed) group
78
Group 1 sample size Number of subjects in the case (exposed) group
87

Lab analysis

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

Statistical Analysis

Statistical test
LEfSe
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)?
No


Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
unchanged
Richness Number of species
unchanged

Signature 1

Reviewed Marked as Reviewed by Fatima on 2021/09/16

Curated date: 2021/05/28

Curator: Claregrieve1

Revision editor(s): Claregrieve1

Source: Table 2

Description: Differential bacterial species abundance between COVID-19 samples and non-COVID-19 samples

Abundance in Group 1: increased abundance in COVID-19 cases

NCBI Links
Phocaeicola dorei
Phocaeicola vulgatus
[Ruminococcus] gnavus
[Ruminococcus] torques
Bacteroides ovatus
Bacteroides caccae
Akkermansia muciniphila

Revision editor(s): Claregrieve1

Signature 2

Reviewed Marked as Reviewed by Fatima on 2021/09/16

Curated date: 2021/05/28

Curator: Claregrieve1

Revision editor(s): Claregrieve1

Source: Table 2

Description: Differential bacterial species abundance between COVID-19 samples and non-COVID-19 samples

Abundance in Group 1: decreased abundance in COVID-19 cases

NCBI Links
Bifidobacterium adolescentis
Eubacterium rectale CAG:36
Ruminococcus bromii
Subdoligranulum
Bifidobacterium pseudocatenulatum
Faecalibacterium prausnitzii
Collinsella aerofaciens
Ruminococcus obeum CAG:39
Dorea longicatena
Coprococcus comes
Dorea formicigenerans

Revision editor(s): Claregrieve1

Experiment 2


Reviewed Marked as Reviewed by Fatima on 2022/04/6

Curated date: 2021/05/30

Curator: Claregrieve1

Revision editor(s): Claregrieve1, WikiWorks

Subjects

Location of subjects
China
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 cases
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Recovered following negative quantitative reverse transcription PCR (RT-qPCR) tests for SARS-CoV-2 RNA in nasopharyngeal swabs
Group 0 sample size Number of subjects in the control (unexposed) group
78
Group 1 sample size Number of subjects in the case (exposed) group
13
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
Patients whose COVID-19 treatment included antibiotics were excluded

Lab analysis

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

Statistical Analysis

Statistical test
LEfSe
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)?
No



Signature 1

Reviewed Marked as Reviewed by Fatima on 2022/04/6

Curated date: 2021/05/30

Curator: Claregrieve1

Revision editor(s): Claregrieve1

Source: Table 3

Description: Differences in gut microbiome bacterial species between feces samples from healthy controls and samples from non-antibiotic-treated patients with COVID-19 after recovery

Abundance in Group 1: increased abundance in Recovered COVID-19 cases

NCBI Links
Bifidobacterium dentium
Dorea longicatena
Enterocloster bolteae
Ligilactobacillus ruminis
Parabacteroides distasonis
Parabacteroides sp.
Prevotella copri
Ruminococcus sp. 5_1_39BFAA
Streptococcus salivarius
Veillonella parvula
[Clostridium] symbiosum

Revision editor(s): Claregrieve1

Signature 2

Reviewed Marked as Reviewed by Fatima on 2022/04/6

Curated date: 2021/05/30

Curator: Claregrieve1

Revision editor(s): Claregrieve1

Source: Table 3

Description: Differences in gut microbiome bacterial species between feces samples from healthy controls and samples from non-antibiotic-treated patients with COVID-19 after recovery

Abundance in Group 1: decreased abundance in Recovered COVID-19 cases

NCBI Links
Alistipes putredinis
Bifidobacterium longum subsp. longum
Bifidobacterium pseudocatenulatum
Collinsella aerofaciens
Coprococcus comes
Dorea formicigenerans
Eubacterium rectale CAG:36
Faecalibacterium prausnitzii
Ruminococcus bromii
Ruminococcus obeum CAG:39
Subdoligranulum

Revision editor(s): Claregrieve1

Experiment 3


Reviewed Marked as Reviewed by Fatima on 2022/04/6

Curated date: 2021/05/30

Curator: Claregrieve1

Revision editor(s): Claregrieve1, WikiWorks

Subjects

Location of subjects
China
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 cases
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Recovered following negative quantitative reverse transcription PCR (RT-qPCR) tests for SARS-CoV-2 RNA in nasopharyngeal swabs, treated with antibiotics during course of COVID-19
Group 0 sample size Number of subjects in the control (unexposed) group
78
Group 1 sample size Number of subjects in the case (exposed) group
14

Lab analysis

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

Statistical Analysis

Statistical test
LEfSe
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)?
No



Signature 1

Reviewed Marked as Reviewed by Fatima on 2022/04/6

Curated date: 2021/05/30

Curator: Claregrieve1

Revision editor(s): Claregrieve1

Source: Table 3

Description: Differences in gut microbiome bacterial species between feces samples from healthy controls and samples from antibiotic-treated patients with COVID-19 after recovery

Abundance in Group 1: increased abundance in Recovered COVID-19 cases

NCBI Links
Bifidobacterium dentium
Ligilactobacillus ruminis
Parabacteroides distasonis
Enterococcus faecalis
Parabacteroides
Enterocloster bolteae
[Clostridium] symbiosum
Veillonella parvula

Revision editor(s): Claregrieve1

Signature 2

Reviewed Marked as Reviewed by Fatima on 2022/04/6

Curated date: 2021/05/30

Curator: Claregrieve1

Revision editor(s): Claregrieve1

Source: Table 3

Description: Differences in gut microbiome bacterial species between feces samples from healthy controls and samples from antibiotic-treated patients with COVID-19 after recovery

Abundance in Group 1: decreased abundance in Recovered COVID-19 cases

NCBI Links
Eubacterium rectale CAG:36
Ruminococcus bromii
Faecalibacterium prausnitzii
Bifidobacterium pseudocatenulatum
Subdoligranulum
Collinsella aerofaciens
Bifidobacterium longum subsp. longum
Ruminococcus sp. 5_1_39BFAA
Ruminococcus obeum CAG:39
Prevotella copri
Coprococcus comes
Dorea formicigenerans
Dorea longicatena
Alistipes putredinis
Streptococcus salivarius
Anaerobutyricum hallii

Revision editor(s): Claregrieve1

Experiment 4


Reviewed Marked as Reviewed by Fatima on 2022/04/6

Curated date: 2021/06/10

Curator: Claregrieve1

Revision editor(s): Claregrieve1, WikiWorks

Subjects

Location of subjects
China
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
COVID-19 patients treated with antibiotics
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Laboratory-confirmed SARS-CoV-2 positive by quantitative reverse transcription PCR performed on nasopharyngeal swabs, treated with antibiotics
Group 0 sample size Number of subjects in the control (unexposed) group
78
Group 1 sample size Number of subjects in the case (exposed) group
34

Lab analysis

Sequencing type
WMS
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)?
No



Signature 1

Reviewed Marked as Reviewed by Fatima on 2022/04/6

Curated date: 2021/06/11

Curator: Claregrieve1

Revision editor(s): Claregrieve1

Source: Table S3

Description: Differential bacterial species abundance between COVID-19 samples from patients were treated with antibiotics and non-COVID-19 samples

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

NCBI Links
Bifidobacterium adolescentis
Dorea formicigenerans
Dorea longicatena
Faecalibacterium prausnitzii
Ruminococcus obeum CAG:39
Subdoligranulum sp.
Klebsiella pneumoniae
Adlercreutzia equolifaciens
Blautia obeum
Clostridium leptum CAG:27
Coprococcus comes
Subdoligranulum sp. 4_3_54A2FAA
Enterococcus avium
Eubacterium ventriosum
Citrobacter sp.

Revision editor(s): Claregrieve1

Signature 2

Reviewed Marked as Reviewed by Fatima on 2022/04/6

Curated date: 2021/06/11

Curator: Claregrieve1

Revision editor(s): Claregrieve1

Source: Table S3

Description: Differential bacterial species abundance between COVID-19 samples from patients were treated with antibiotics and non-COVID-19 samples

Abundance in Group 1: increased abundance in COVID-19 patients treated with antibiotics

NCBI Links
Anaerobutyricum hallii
Bacteroides caccae
Bacteroides ovatus
Ruminococcus sp. 5_1_39BFAA
Scardovia inopinata
Cutibacterium acnes
Cryptobacterium curtum
Shuttleworthia satelles
Parascardovia denticolens
Enterococcus gallinarum
Lachnoanaerobaculum sp. ICM7
Oribacterium sp. oral taxon 078
Lachnospiraceae bacterium 5_1_63FAA
Slackia sp.
Olsenella profusa
Coprococcus catus
Lancefieldella rimae
Staphylococcus aureus
Rothia aeria
Abiotrophia defectiva
Roseburia inulinivorans
Stomatobaculum longum
Staphylococcus epidermidis
Anaerostipes hadrus
Eubacterium ramulus
Scardovia wiggsiae
Sutterella wadsworthensis
Alistipes onderdonkii
unclassified Coprobacillus
Olsenella uli
Parabacteroides sp.

Revision editor(s): Claregrieve1