Gut microbiota composition reflects disease severity and dysfunctional immune responses in patients with COVID-19
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Study information
-
Quality control
- Retracted paper
- Contamination issues suspected
- Batch effect issues suspected
- Uncontrolled confounding suspected
- Results are suspect (various reasons)
- Tags applied
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
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
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
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
Revision editor(s): Claregrieve1
Experiment 2
Reviewed Marked as Reviewed by Fatima on 2022/04/6
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
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
Revision editor(s): Claregrieve1
Signature 2
Reviewed Marked as Reviewed by Fatima on 2022/04/6
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
Revision editor(s): Claregrieve1
Experiment 3
Reviewed Marked as Reviewed by Fatima on 2022/04/6
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
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
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
Revision editor(s): Claregrieve1
Experiment 4
Reviewed Marked as Reviewed by Fatima on 2022/04/6
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
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
Revision editor(s): Claregrieve1
Signature 2
Reviewed Marked as Reviewed by Fatima on 2022/04/6
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
Revision editor(s): Claregrieve1
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