Gut Microbiota Dysbiosis Correlates with Abnormal Immune Response in Moderate COVID-19 Patients with Fever

From BugSigDB
Reviewed Marked as Reviewed by Fatima on 2022/05/18
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Zhou Y, Shi X, Fu W, Xiang F, He X, Yang B, Wang X, Ma WL
Journal
Journal of inflammation research
Year
2021
Keywords:
epitopes, fever, gut microbiota, moderate COVID-19, shotgun metagenomic sequencing
Background: Most COVID-19 patients are moderate, and fever is the most common clinical manifestation and associated with poorer prognosis. Gut microbiota may also play important roles in COVID-19 pathogenesis. However, the association between gut microbiota and fever in individuals with moderate COVID-19 remains unclear. Methods: We compared the clinical features and laboratory results of 187 moderate COVID-19 patients with fever and without fever and identified several inflammatory markers in patients with fever. Then, we performed gut metagenome-wide association study for 31 individuals to identify the microbes and their epitopes which have potential role in fever and hyperinflammation. Results: Among 187 moderate COVID-19 patients, 127 (67.9%) patients presented with fever. Lymphocytes, CD3+ T cells, CD4+ T cells and the ratio of CD4+ T cells to CD8+ T cells were significantly reduced, while AST, LDH, CRP, IL-6 and IL-10 were significantly elevated in patients with fever. Gut microbiome composition was significantly altered in patients with fever compared with those with non-fever. Opportunistic pathogens such as Enterococcus faecalis and Saccharomyces cerevisiae were enriched in patients with fever. E. faecalis was positively correlated with LDH and D-dimer and negatively correlated with CD8+T cells and IL-4, while S. cerevisiae was positively correlated with diarrhea symptom. Furthermore, several species with anti-inflammatory and protective effects, such as Bacteroides fragilis and Eubacterium ramulus, were enriched in patients with non-fever. B. fragilis was positively correlated with lymphocytes, and E. ramulus was negatively correlated with LDH, AST and IL-6. Finally, we found that several bacterial epitopes of GroEL, a homolog of human HSP60, were enriched in patients with fever and positively correlated with IL-6, IL-10, WBC, neutrophils, D-dimer, LDH, CRP, and E. faecalis. Conclusion: Gut microbiota dysbiosis correlates with abnormal immune response in moderate COVID-19 patients with fever.

Experiment 1


Reviewed Marked as Reviewed by Fatima on 2022/05/18

Curated date: 2021/07/03

Curator: Claregrieve1

Revision editor(s): Claregrieve1, WikiWorks

Subjects

Location of subjects
China
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
COVID-19 patients without fever
Group 1 name Corresponds to the case (exposed) group for case-control studies
COVID-19 patients with fever
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Symptomatic patients with confirmed COVID-19 (positive for COVID-19 nucleic acid by real-time RT-PCR from throat swab specimens) and fever (axillary temperature > 37.3 degrees Celsius)
Group 0 sample size Number of subjects in the control (unexposed) group
11
Group 1 sample size Number of subjects in the case (exposed) group
20

Lab analysis

Sequencing type
WMS
16S variable region One or more hypervariable region(s) of the bacterial 16S gene
Not specified
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)?
No
LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
2

Alpha Diversity

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

Signature 1

Reviewed Marked as Reviewed by Fatima on 2022/05/18

Curated date: 2021/07/03

Curator: Claregrieve1

Revision editor(s): Claregrieve1

Source: Figure 2

Description: Differential microbial abundance between COVID-19 patients with fever and COVID-19 patients without fever

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

NCBI Quality ControlLinks
Saccharomyces
Enterococcus

Revision editor(s): Claregrieve1

Signature 2

Reviewed Marked as Reviewed by Fatima on 2022/05/18

Curated date: 2021/07/03

Curator: Claregrieve1

Revision editor(s): Claregrieve1

Source: Figure 2

Description: Differential microbial abundance between COVID-19 patients with fever and COVID-19 patients without fever

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

NCBI Quality ControlLinks
Anaerostipes
Prevotella
Parabacteroides
Phascolarctobacterium
Eggerthella

Revision editor(s): Claregrieve1

Experiment 2


Reviewed Marked as Reviewed by Fatima on 2022/05/18

Curated date: 2021/07/03

Curator: Claregrieve1

Revision editor(s): Claregrieve1, WikiWorks

Differences from previous experiment shown

Subjects

Lab analysis

Statistical Analysis

Statistical test
Mann-Whitney (Wilcoxon)
LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
Not specified

Alpha Diversity

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

Signature 1

Reviewed Marked as Reviewed by Fatima on 2022/05/18

Curated date: 2021/07/03

Curator: Claregrieve1

Revision editor(s): Claregrieve1

Source: Table S5-7

Description: Differential microbial abundance between COVID-19 patients with fever and COVID-19 patients without fever

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

NCBI Quality ControlLinks
Ascomycota
Enterococcus
Citrobacter
Saccharomyces
Haemophilus
Enterocloster bolteae
Saccharomyces cerevisiae
Haemophilus parainfluenzae
Citrobacter freundii
Citrobacter sp.
Enterococcus faecalis

Revision editor(s): Claregrieve1

Signature 2

Reviewed Marked as Reviewed by Fatima on 2022/05/18

Curated date: 2021/07/03

Curator: Claregrieve1

Revision editor(s): Claregrieve1

Source: Tables S5-7

Description: Differential microbial abundance between COVID-19 patients with fever and COVID-19 patients without fever

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

NCBI Quality ControlLinks
Parasutterella
Gordonibacter
Alistipes shahii
Lachnospiraceae bacterium 7_1_58FAA
Erysipelotrichaceae bacterium 6_1_45
Bacteroides thetaiotaomicron
Bacteroides fragilis
Bacteroides cellulosilyticus
Bacteroides xylanisolvens
Lachnospiraceae bacterium 3_1_57FAA_CT1
Eubacterium ramulus
Parasutterella excrementihominis
Phocaeicola vulgatus
Anaerostipes hadrus
Burkholderiales bacterium 1_1_47
Lachnospiraceae bacterium 5_1_63FAA
Lachnospiraceae bacterium 2_1_58FAA

Revision editor(s): Claregrieve1