Temporal changes in fecal microbiota of patients infected with COVID-19: a longitudinal cohort

Study information

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Reviewed Marked as Reviewed by Peace Sandy on 2024-2-22

study design

time series / longitudinal observational

Citation

PMID PubMed identifier for scientific articles.

37596518

DOI Digital object identifier for electronic documents.

https://doi.org/10.1186/s12879-023-08511-6

URI

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10436399/

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

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Reviewed Marked as Reviewed by Peace Sandy on 2024-2-22

Curated date: 2023/10/14

Curator: Tolulopeo

Revision editor(s): Tolulopeo, Peace Sandy, Svetlana up

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,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,cOVID-19

Group 0 name Corresponds to the control (unexposed) group for case-control studies

Non-Covid 19 Patients - pneumonia 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

Patients admitted for COVID-19

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)

3 Months

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)

0.05

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

2.5

Alpha Diversity

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

decreased

Chao1 Abundance-based estimator of species richness

unchanged

Signature 1

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Reviewed Marked as Reviewed by Peace Sandy on 2024-2-22

Curated date: 2023/10/15

Curator: Tolulopeo

Revision editor(s): Tolulopeo, Peace Sandy

Source: Fig. 1C

Description: C, D Differential abundance analysis and distance-based redundancy analysis (db-RDA) in COVID-19 and non-COVID-19 patients. COVID-19 and non-COVID-19 pneumonia patients were compared to evaluate the COVID-19 effect. C Differentially abundant taxa identified by linear discriminant analysis effect size (LEfSe) at genus level. The results with p-value < 0.01 and effect size (log10) > 2.5 for each group are presented as a bar plot (**p < 0.01, ***p < 0.001).

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

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Bacteroides
Pseudoflavonifractor
Ruthenibacterium

Revision editor(s): Tolulopeo, Peace Sandy

Signature 2

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Reviewed Marked as Reviewed by Peace Sandy on 2024-2-22

Curated date: 2023/10/15

Curator: Tolulopeo

Revision editor(s): Tolulopeo, Peace Sandy

Source: Fig. 1c

Description: C, D Differential abundance analysis and distance-based redundancy analysis (db-RDA) in COVID-19 and non-COVID-19 patients. COVID-19 and non-COVID-19 pneumonia patients were compared to evaluate the COVID-19 effect. C Differentially abundant taxa identified by linear discriminant analysis effect size (LEfSe) at genus level. The results with p-value < 0.01 and effect size (log10) > 2.5 for each group are presented as a bar plot (**p < 0.01, ***p < 0.001).

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

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Fenollaria
Finegoldia
Porphyromonas
Corynebacterium
Sutterella
Anaerococcus
Negativicoccus

Revision editor(s): Tolulopeo, Peace Sandy

Experiment 2

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Reviewed Marked as Reviewed by Peace Sandy on 2024-2-22

Curated date: 2023/10/14

Curator: Tolulopeo

Revision editor(s): Tolulopeo, Peace Sandy, Svetlana up

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies

COVID-19 patients - Non-Ventilated

Group 1 name Corresponds to the case (exposed) group for case-control studies

COVID-19 patients - Ventilated

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group

COVID-19 patients in Intensive Care Unit [ICU] - Ventilated

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

Lab analysis

Statistical Analysis

Alpha Diversity

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

unchanged

Signature 1

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Reviewed Marked as Reviewed by Peace Sandy on 2024-2-22

Curated date: 2023/10/16

Curator: Tolulopeo

Revision editor(s): Tolulopeo, Davvve, Peace Sandy

Source: Fig 2 A

Description: Impact of COVID-19 severity on the taxa composition and longitudinal changes of the gut microbiota. A, B Differential abundance analysis and db-RDA analysis in ventilated and non-ventilated COVID-19 patients. A Genera differentially abundant among the two groups were identified by a complex model including ventilation, antibiotics and timepoint with longitudinal sampling correction using negative binomial and zero-inflated mixed model (NBZIMM). The taxa with p-value < 0.01 and effect size (log10) > 2.5 for each group are presented in the bar plot (**p < 0.01, ***p < 0.001).

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

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Campylobacter
Ruminococcus
Clostridium

Revision editor(s): Tolulopeo, Davvve, Peace Sandy

Signature 2

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Curated date: 2023/10/16

Curator: Tolulopeo

Revision editor(s): Tolulopeo, Peace Sandy

Source: Fig 2 A

Description: Impact of COVID-19 severity on the taxa composition and longitudinal changes of the gut microbiota. A, B Differential abundance analysis and db-RDA analysis in ventilated and non-ventilated COVID-19 patients. A Genera differentially abundant among the two groups were identified by a complex model including ventilation, antibiotics and timepoint with longitudinal sampling correction using negative binomial and zero-inflated mixed model (NBZIMM). The taxa with p-value < 0.01 and effect size (log10) > 2.5 for each group are presented in the bar plot (**p < 0.01, ***p < 0.001).

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

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Streptococcus
Faecalibacterium
Roseburia

Revision editor(s): Tolulopeo, Peace Sandy