Alterations of the Gut Microbiota in Patients With Coronavirus Disease 2019 or H1N1 Influenza

From BugSigDB
Reviewed Marked as Reviewed by Fatima on 2021/07/28
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI Uniform resource identifier for web resources.
Authors
Gu S, Chen Y, Wu Z, Chen Y, Gao H, Lv L, Guo F, Zhang X, Luo R, Huang C, Lu H, Zheng B, Zhang J, Yan R, Zhang H, Jiang H, Xu Q, Guo J, Gong Y, Tang L, Li L
Journal
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
Year
2020
BACKGROUND: Coronavirus disease 2019 (COVID-19) is an emerging serious global health problem. Gastrointestinal symptoms are common in COVID-19 patients, and severe acute respiratory syndrome coronavirus 2 RNA has been detected in stool specimens. However, the relationship between the gut microbiome and disease remains to be established. METHODS: We conducted a cross-sectional study of 30 patients with COVID-19, 24 patients with influenza A(H1N1), and 30 matched healthy controls (HCs) to identify differences in the gut microbiota by 16S ribosomal RNA gene V3-V4 region sequencing. RESULTS: Compared with HCs, COVID-19 patients had significantly reduced bacterial diversity; a significantly higher relative abundance of opportunistic pathogens, such as Streptococcus, Rothia, Veillonella, and Actinomyces; and a lower relative abundance of beneficial symbionts. Five biomarkers showed high accuracy for distinguishing COVID-19 patients from HCs with an area under the curve (AUC) up to 0.89. Patients with H1N1 displayed lower diversity and different overall microbial composition compared with COVID-19 patients. Seven biomarkers were selected to distinguish the 2 cohorts (AUC = 0.94). CONCLUSIONS: The gut microbial signature of patients with COVID-19 was different from that of H1N1 patients and HCs. Our study suggests the potential value of the gut microbiota as a diagnostic biomarker and therapeutic target for COVID-19, but further validation is needed.

Experiment 1


Reviewed Marked as Reviewed by Fatima on 2021/06/30

Curated date: 2021/06/03

Curator: Claregrieve1

Revision editor(s): Fatima, 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
viral COVID-19 infections confirmed by real-time reverse-transcription polymerase chain reaction
Group 0 sample size Number of subjects in the control (unexposed) group
30
Group 1 sample size Number of subjects in the case (exposed) group
30
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
4 weeks

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
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
LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
3.5
Matched on Factors on which subjects have been matched on in a case-control study
age, body mass index, sex

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
decreased
Chao1 Abundance-based estimator of species richness
decreased

Signature 1

Reviewed Marked as Reviewed by Fatima on 2021/06/30

Curated date: 2021/06/03

Curator: Claregrieve1

Revision editor(s): Claregrieve1

Source: Figure 3a

Description: Differences in microbial composition between patients with coronavirus disease 2019 and healthy controls

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

NCBI Links
Streptococcus
Rothia
Veillonella
Thomasclavelia
Actinomyces

Revision editor(s): Claregrieve1

Signature 2

Reviewed Marked as Reviewed by Fatima on 2021/06/30

Curated date: 2021/06/03

Curator: Claregrieve1

Revision editor(s): Fatima, Claregrieve1

Source: Figure 3a

Description: Differences in microbial composition between patients with coronavirus disease 2019 and healthy controls

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

NCBI Links
Agathobacter
Anaerobutyricum hallii
Anaerostipes
Dorea
Faecalibacterium
Fusicatenibacter
Intestinibacter
Klebsiella
Romboutsia
Turicibacter
[Ruminococcus] torques
Clostridium

Revision editor(s): Fatima, Claregrieve1

Experiment 2


Reviewed Marked as Reviewed by Fatima on 2021/07/16

Curated date: 2021/06/03

Curator: Claregrieve1

Revision editor(s): LGeistlinger, 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
influenza A (H1N1) influenza A (H1N1)
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
H1N1 cases
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
H1N1 patients with viral infection confirmed by real-time reverse-transcription polymerase chain reaction hospitalized between January 2018 and March 2019 with severe disease at time of admission
Group 0 sample size Number of subjects in the control (unexposed) group
30
Group 1 sample size Number of subjects in the case (exposed) group
24
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
4 weeks

Lab analysis

Sequencing type
16S
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)?
Yes
LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
3.5
Matched on Factors on which subjects have been matched on in a case-control study
age, body mass index, sex

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
decreased
Chao1 Abundance-based estimator of species richness
decreased

Signature 1

Needs review

Curated date: 2021/06/03

Curator: Claregrieve1

Revision editor(s): Claregrieve1

Source: Supplementary Figure 2

Description: Comparison of estimated fecal microbiome phylotypes in H1N1 patients and healthy controls

Abundance in Group 1: decreased abundance in H1N1 cases

NCBI Links
Blautia
Romboutsia
Collinsella
Anaerobutyricum hallii
Bifidobacterium
Agathobacter
Fusicatenibacter
[Ruminococcus] torques
Anaerostipes
Dorea
Ruminococcus sp.

Revision editor(s): Claregrieve1

Signature 2

Needs review

Curated date: 2021/06/03

Curator: Claregrieve1

Revision editor(s): Claregrieve1

Source: Supplementary Figure 2

Description: Comparison of estimated fecal microbiome phylotypes in H1N1 patients and healthy controls

Abundance in Group 1: increased abundance in H1N1 cases

NCBI Links
Enterococcus
Prevotella
Finegoldia
Peptoniphilus

Revision editor(s): Claregrieve1

Experiment 3


Reviewed Marked as Reviewed by Fatima on 2021/06/30

Curated date: 2021/06/03

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
H1N1 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
viral COVID-19 infections confirmed by real-time reverse-transcription polymerase chain reaction
Group 0 sample size Number of subjects in the control (unexposed) group
24
Group 1 sample size Number of subjects in the case (exposed) group
30
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
subjects who received antibiotics and/or probiotics within 4 weeks of enrollment were excluded

Lab analysis

Sequencing type
16S
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)?
Yes
LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
3.5


Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
increased
Chao1 Abundance-based estimator of species richness
increased

Signature 1

Reviewed Marked as Reviewed by Fatima on 2021/06/30

Curated date: 2021/06/03

Curator: Claregrieve1

Revision editor(s): Fatima, Claregrieve1

Source: Figure 4a

Description: Differences in microbiota composition between COVID-19 patients and H1N1 patients

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

NCBI Links
Agathobacter
Anaerobutyricum hallii
Anaerostipes
Bifidobacterium
Blautia
Collinsella
Dorea
Fusicatenibacter
Lachnospiraceae
Rothia
Ruminococcus
Streptococcus
[Ruminococcus] gnavus
[Ruminococcus] torques
Clostridium

Revision editor(s): Fatima, Claregrieve1

Signature 2

Reviewed Marked as Reviewed by Fatima on 2021/06/30

Curated date: 2021/06/03

Curator: Claregrieve1

Revision editor(s): Claregrieve1

Source: Figure 4a

Description: Differences in microbiota composition between COVID-19 patients and H1N1 patients

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

NCBI Links
Prevotella
Ezakiella
Akkermansia
Murdochiella
Porphyromonas

Revision editor(s): Claregrieve1

Experiment 4


Needs review

Curated date: 2021/06/30

Curator: Fatima

Revision editor(s): Fatima, 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
viral COVID-19 infections confirmed by real-time reverse-transcription polymerase chain reaction
Group 0 sample size Number of subjects in the control (unexposed) group
30
Group 1 sample size Number of subjects in the case (exposed) group
30
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
4 weeks

Lab analysis

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

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
Matched on Factors on which subjects have been matched on in a case-control study
age, body mass index, sex

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
decreased
Chao1 Abundance-based estimator of species richness
decreased

Signature 1

Needs review

Curated date: 2021/06/30

Curator: Fatima

Revision editor(s): Fatima

Source: Figure 2A, 2B, 2C, 2D

Description: Taxonomic differences in fecal microbiota between patients with covid-19 and healthy controls

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

NCBI Links
Streptococcaceae
Streptococcus
Bacilli

Revision editor(s): Fatima