Temporal changes in fecal microbiota of patients infected with COVID-19: a longitudinal cohort
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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.
Authors
Galperine T, Choi Y, Pagani JL, Kritikos A, Papadimitriou-Olivgeris M, Méan M, Scherz V, Opota O, Greub G, Guery B, Bertelli C
Journal
BMC infectious diseases
Year
2023
Keywords:
COVID-19, Gut microbiota, Gut-lung axis, Microbiota profiling, SARS-CoV-2
BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a multifaceted disease potentially responsible for various clinical manifestations including gastro-intestinal symptoms. Several evidences suggest that the intestine is a critical site of immune cell development, gut microbiota could therefore play a key role in lung immune response. We designed a monocentric longitudinal observational study to describe the gut microbiota profile in COVID-19 patients and compare it to a pre-existing cohort of ventilated non-COVID-19 patients. METHODS: From March to December 2020, we included patients admitted for COVID-19 in medicine (43 not ventilated) or intensive care unit (ICU) (14 ventilated) with a positive SARS-CoV-2 RT-PCR assay in a respiratory tract sample. 16S metagenomics was performed on rectal swabs from these 57 COVID-19 patients, 35 with one and 22 with multiple stool collections. Nineteen non-COVID-19 ICU controls were also enrolled, among which 14 developed ventilator-associated pneumonia (pneumonia group) and five remained without infection (control group). SARS-CoV-2 viral loads in fecal samples were measured by qPCR. RESULTS: Although similar at inclusion, Shannon alpha diversity appeared significantly lower in COVID-19 and pneumonia groups than in the control group at day 7. Furthermore, the microbiota composition became distinct between COVID-19 and non-COVID-19 groups. The fecal microbiota of COVID-19 patients was characterized by increased Bacteroides and the pneumonia group by Prevotella. In a distance-based redundancy analysis, only COVID-19 presented significant effects on the microbiota composition. Moreover, patients in ICU harbored increased Campylobacter and decreased butyrate-producing bacteria, such as Lachnospiraceae, Roseburia and Faecalibacterium as compared to patients in medicine. Both the stay in ICU and patient were significant factors affecting the microbiota composition. SARS-CoV-2 viral loads were higher in ICU than in non-ICU patients. CONCLUSIONS: Overall, we identified distinct characteristics of the gut microbiota in COVID-19 patients compared to control groups. COVID-19 patients were primarily characterized by increased Bacteroides and decreased Prevotella. Moreover, disease severity showed a negative correlation with butyrate-producing bacteria. These features could offer valuable insights into potential targets for modulating the host response through the microbiota and contribute to a better understanding of the disease's pathophysiology. TRIAL REGISTRATION: CER-VD 2020-00755 (05.05.2020) & 2017-01820 (08.06.2018).
Experiment 1
Subjects
- Location of subjects
- Switzerland
- Host species Species from which microbiome was sampled. Contact us to have more species added.
- 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
- ventilator-associated pneumonia (pneumonia group)
- 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
- Patients admitted for COVID-19 in medicine (43 not ventilated) or intensive care unit (ICU) (14 ventilated) with a positive SARS-CoV-2 RT-PCR assay in a respiratory tract sample
- Group 0 sample size Number of subjects in the control (unexposed) group
- 19
- Group 1 sample size Number of subjects in the case (exposed) group
- 57
- Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
- 3months
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
- Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
- relative abundances
- Statistical test
- LEfSe
- Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
- 0.036
- MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
- No
- LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
- 2.5
- Matched on Factors on which subjects have been matched on in a case-control study
- age, sex, Matched on: "height" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.height, Matched on: "weight" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.weight, Matched on: "Charlson Comorbidities Index (CCI)" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.Charlson Comorbidities Index (CCI)
- Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
- antibiotic, Confounders controlled for: "timepoint" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.timepoint, Confounders controlled for: "ventilation" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.ventilation
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- decreased
Signature 1
Source: Fig. 1C
Description: Differentially abundant genera in the COVID-19 group compared to the pneumonia group
Abundance in Group 1: increased abundance in COVID-19 Patients
| NCBI | Quality Control | Links |
|---|---|---|
| Bacteroides | ||
| Ruthenibacterium | ||
| Pseudoflavonifractor |
Revision editor(s): Tolulopeo
Signature 2
Source: Fig. 1c
Description: Differentially abundant genera in the pneumonia group compared to the COVID-19 group
Abundance in Group 1: increased abundance in COVID-19 Patients
| NCBI | Quality Control | Links |
|---|---|---|
| Prevotella | ||
| Finegoldia | ||
| Fenollaria | ||
| Peptoniphilus | ||
| Porphyromonas |
Revision editor(s): Tolulopeo
Experiment 2
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- COVID-19 patients without ventilation
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- COVID-19 patients with ventilation
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Intubated COVID-19 patients
- Group 0 sample size Number of subjects in the control (unexposed) group
- 43
- Group 1 sample size Number of subjects in the case (exposed) group
- 14
- Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
- 3 months
Lab analysis
Statistical Analysis
- Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
- 2.5
- MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
- Not specified
- LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
- Not specified
- Matched on Factors on which subjects have been matched on in a case-control study
- age, body mass index, Matched on: "Charlson Comorbidity Index (CCI)" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.Charlson Comorbidity Index (CCI)
- Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
- antibiotic, Confounders controlled for: "Timepoint" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.Timepoint, Confounders controlled for: "Ventilation" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.Ventilation
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
Signature 1
Source: Fig 2 A
Description: Impact of COVID-19 severity on the taxa composition and longitudinal changes of the gut microbiota.
Abundance in Group 1: decreased abundance in COVID-19 patients with ventilation
| NCBI | Quality Control | Links |
|---|---|---|
| Faecalibacterium | ||
| Roseburia | ||
| Streptococcus | ||
| Lachnospiraceae incertae sedis |
Signature 2
Source: Fig 2 A
Description: The impact of COVID-19 severity on the taxa composition and longitudinal changes of the gut microbiota
Abundance in Group 1: increased abundance in COVID-19 patients with ventilation
| NCBI | Quality Control | Links |
|---|---|---|
| Campylobacter | ||
| Clostridium | ||
| Ruminococcus |
Revision editor(s): Tolulopeo
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