Metagenomic analysis reveals oropharyngeal microbiota alterations in patients with COVID-19

From BugSigDB
Needs review
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI Uniform resource identifier for web resources.
Authors
Ma S, Zhang F, Zhou F, Li H, Ge W, Gan R, Nie H, Li B, Wang Y, Wu M, Li D, Wang D, Wang Z, You Y, Huang Z
Journal
Signal transduction and targeted therapy
Year
2021
COVID-19 remains a serious emerging global health problem, and little is known about the role of oropharynx commensal microbes in infection susceptibility and severity. Here, we present the oropharyngeal microbiota characteristics identified by shotgun metagenomic sequencing analyses of oropharynx swab specimens from 31 COVID-19 patients, 29 influenza B patients, and 28 healthy controls. Our results revealed a distinct oropharyngeal microbiota composition in the COVID-19 patients, characterized by enrichment of opportunistic pathogens such as Veillonella and Megasphaera and depletion of Pseudopropionibacterium, Rothia, and Streptococcus. Based on the relative abundance of the oropharyngeal microbiome, we built a microbial classifier to distinguish COVID-19 patients from flu patients and healthy controls with an AUC of 0.889, in which Veillonella was identified as the most prominent biomarker for COVID-19 group. Several members of the genus Veillonella, especially Veillonella parvula which was highly enriched in the oropharynx of our COVID-19 patients, were also overrepresented in the BALF of COVID-19 patients, indicating that the oral cavity acts as a natural reservoir for pathogens to induce co-infections in the lungs of COVID-19 patients. We also found the increased ratios of Klebsiella sp., Acinetobacter sp., and Serratia sp. were correlated with both disease severity and elevated systemic inflammation markers (neutrophil-lymphocyte ratio, NLR), suggesting that these oropharynx microbiota alterations may impact COVID-19 severity by influencing the inflammatory response. Moreover, the oropharyngeal microbiome of COVID-19 patients exhibited a significant enrichment in amino acid metabolism and xenobiotic biodegradation and metabolism. In addition, all 26 drug classes of antimicrobial resistance genes were detected in the COVID-19 group, and were significantly enriched in critical cases. In conclusion, we found that oropharyngeal microbiota alterations and functional differences were associated with COVID-19 severity.

Experiment 1


Needs review

Curated date: 2021/06/30

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
Oropharynx Mesopharynx,Oral part of pharynx,Pars oralis pharyngis,Oropharynx
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
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Confirmed COVID-19 cases
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
31

Lab analysis

Sequencing type
WMS
Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
MGISEQ-2000

Statistical Analysis

Statistical test
Mann-Whitney (Wilcoxon)
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



Signature 1

Needs review

Curated date: 2021/07/13

Curator: Claregrieve1

Revision editor(s): Claregrieve1

Source: Figure 4c

Description: Differential microbial abundance between COVID-19 patients and healthy controls

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

NCBI Links
Arachnia
Mobiluncus
Oribacterium
Oribacterium sp. oral taxon 108
Rothia
Rothia sp. HSID18069
Slackia
Arachnia propionica

Revision editor(s): Claregrieve1

Signature 2

Needs review

Curated date: 2021/07/14

Curator: Claregrieve1

Revision editor(s): Claregrieve1

Source: Figure 4c

Description: Differential microbial abundance between COVID-19 patients and healthy controls

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

NCBI Links
Veillonella
Liquorilactobacillus nagelii

Revision editor(s): Claregrieve1

Experiment 2


Needs review

Curated date: 2021/07/14

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
Oropharynx Mesopharynx,Oral part of pharynx,Pars oralis pharyngis,Oropharynx
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
Flu patients
Group 1 name Corresponds to the case (exposed) group for case-control studies
COVID-19 patients
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Confirmed COVID-19 cases
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
31

Lab analysis

Sequencing type
WMS
Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
MGISEQ-2000

Statistical Analysis

Statistical test
Mann-Whitney (Wilcoxon)
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



Signature 1

Needs review

Curated date: 2021/07/14

Curator: Claregrieve1

Revision editor(s): Claregrieve1

Source: Figure 4c

Description: Differential microbial abundance between COVID-19 patients and other flu patients

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

NCBI Links
Arachnia
Limosilactobacillus fermentum
Oribacterium
Oribacterium sp. oral taxon 108
Prevotella amnii
Rothia
Rothia sp. HSID18069
Slackia
Arachnia propionica

Revision editor(s): Claregrieve1

Experiment 3


Needs review

Curated date: 2021/07/14

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
Oropharynx Mesopharynx,Oral part of pharynx,Pars oralis pharyngis,Oropharynx
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
Flu patients
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patients with influenza B
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
31

Lab analysis

Sequencing type
WMS
Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
MGISEQ-2000

Statistical Analysis

Statistical test
Mann-Whitney (Wilcoxon)
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

Shannon Estimator of species richness and species evenness: more weight on species richness
increased

Signature 1

Needs review

Curated date: 2021/07/14

Curator: Claregrieve1

Revision editor(s): Claregrieve1

Source: Figure 4c

Description: Differential microbial abundance between flu patients and healthy controls

Abundance in Group 1: increased abundance in Flu patients

NCBI Links
Veillonella
Liquorilactobacillus nagelii
Limosilactobacillus fermentum
Prevotella amnii

Revision editor(s): Claregrieve1

Signature 2

Needs review

Curated date: 2021/07/14

Curator: Claregrieve1

Revision editor(s): Claregrieve1

Source: Figure 4c

Description: Differential microbial abundance between flu patients and healthy controls

Abundance in Group 1: decreased abundance in Flu patients

NCBI Links
Oribacterium
Arachnia
Rothia
Mobiluncus
Rothia sp. HSID18069
Oribacterium sp. oral taxon 108
Arachnia propionica

Revision editor(s): Claregrieve1

Experiment 4


Needs review

Curated date: 2021/07/14

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
Oropharynx Mesopharynx,Oral part of pharynx,Pars oralis pharyngis,Oropharynx
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
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Confirmed COVID-19 cases
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
31

Lab analysis

Sequencing type
WMS
Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
MGISEQ-2000

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)?
Yes



Signature 1

Needs review

Curated date: 2021/07/14

Curator: Claregrieve1

Revision editor(s): Claregrieve1

Source: Figure 2a-b

Description: Differential microbial abundance between COVID-19 patients and healthy controls by LefSe

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

NCBI Links
Actinobaculum
Bifidobacterium
Bulleidia
Cellulomonas
Corynebacterium
Cryptobacterium
Filifactor
Kytococcus
Lachnoanaerobaculum
Mogibacterium
Parvimonas
Propionibacterium
Schaalia
Selenomonas
Streptococcus
Actinomyces
Rothia
Oribacterium
Xylanimonas
Arachnia
Cardiobacterium
Varibaculum
Mobiluncus

Revision editor(s): Claregrieve1

Signature 2

Needs review

Curated date: 2021/07/14

Curator: Claregrieve1

Revision editor(s): Claregrieve1

Source: Figure 2a-b

Description: Differential microbial abundance between COVID-19 patients and healthy controls by LefSe

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

NCBI Links
Megasphaera
Veillonella
Abiotrophia

Revision editor(s): Claregrieve1

Experiment 5


Needs review

Curated date: 2021/07/14

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
Oropharynx Mesopharynx,Oral part of pharynx,Pars oralis pharyngis,Oropharynx
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
Flu patients
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patients with influenza B
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
29

Lab analysis

Sequencing type
WMS
Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
MGISEQ-2000

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)?
Yes



Signature 1

Needs review

Curated date: 2021/07/14

Curator: Claregrieve1

Revision editor(s): Claregrieve1

Source: Figure 2a

Description: Differential microbial abundance between flu patients and healthy controls by LefSe

Abundance in Group 1: decreased abundance in Flu patients

NCBI Links
Streptococcus
Actinomyces
Rothia
Oribacterium
Xylanimonas
Arachnia
Cardiobacterium
Varibaculum

Revision editor(s): Claregrieve1

Signature 2

Needs review

Curated date: 2021/07/14

Curator: Claregrieve1

Revision editor(s): Claregrieve1

Source: Figure 2a

Description: Differential microbial abundance between flu patients and healthy controls by LefSe

Abundance in Group 1: increased abundance in Flu patients

NCBI Links
Megasphaera
Veillonella

Revision editor(s): Claregrieve1