Respiratory Tract Dysbiosis Is Associated with Worse Outcomes in Mechanically Ventilated Patients
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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
Kitsios GD, Yang H, Yang L, Qin S, Fitch A, Wang XH, Fair K, Evankovich J, Bain W, Shah F, Li K, Methé B, Benos PV, Morris A, McVerry BJ
Journal
American journal of respiratory and critical care medicine
Year
2020
Keywords:
acute respiratory distress syndrome, bacterial infections, endotypes, inflammation, microbiota
Rationale: Host inflammatory responses have been strongly associated with adverse outcomes in critically ill patients, but the biologic underpinnings of such heterogeneous responses have not been defined.Objectives: We examined whether respiratory tract microbiome profiles are associated with host inflammation and clinical outcomes of acute respiratory failure.Methods: We collected oral swabs, endotracheal aspirates (ETAs), and plasma samples from mechanically ventilated patients. We performed 16S ribosomal RNA gene sequencing to characterize upper and lower respiratory tract microbiota and classified patients into host-response subphenotypes on the basis of clinical variables and plasma biomarkers of innate immunity and inflammation. We derived diversity metrics and composition clusters with Dirichlet multinomial models and examined our data for associations with subphenotypes and clinical outcomes.Measurements and Main Results: Oral and ETA microbial communities from 301 mechanically ventilated subjects had substantial heterogeneity in α and β diversity. Dirichlet multinomial models revealed a cluster with low α diversity and enrichment for pathogens (e.g., high Staphylococcus or Pseudomonadaceae relative abundance) in 35% of ETA samples, associated with a hyperinflammatory subphenotype, worse 30-day survival, and longer time to liberation from mechanical ventilation (adjusted P < 0.05), compared with patients with higher α diversity and relative abundance of typical oral microbiota. Patients with evidence of dysbiosis (low α diversity and low relative abundance of "protective" oral-origin commensal bacteria) in both oral and ETA samples (17%, combined dysbiosis) had significantly worse 30-day survival and longer time to liberation from mechanical ventilation than patients without dysbiosis (55%; adjusted P < 0.05).Conclusions: Respiratory tract dysbiosis may represent an important, modifiable contributor to patient-level heterogeneity in systemic inflammatory responses and clinical outcomes.
Experiment 1
Reviewed Marked as Reviewed by Folakunmi on 2024-3-4
Curated date: 2023/03/12
Curator: Dherahrose
Revision editor(s): LGeistlinger, Chloe, Dherahrose, Atrayees, Davvve, Folakunmi
Subjects
- Location of subjects
- United States of America
- 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
- Posterior wall of oropharynx Posterior wall of oropharynx,posterior wall of oropharynx
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- Acute respiratory distress syndrome acute lung injury,acute respiratory distress syndrome,ALI,ARDS,increased-permeability pulmonary edema,non-cardiogenic pulmonary edema,Shock lung,shock lung,Stiff lung,Acute respiratory distress syndrome
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Hyper-inflammatory subphenotype and ventilation-free days(VFDs)
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Mortality
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- patients stratified on the basis of 30-day mortality [survivors vs. non-survivors], for whom respiratory specimen cultures were reported as negative (no growth or only normal respiratory flora detected, n=152) as well as those for whom no cultures were obtained (n=76)
- Group 0 sample size Number of subjects in the control (unexposed) group
- 228
- Group 1 sample size Number of subjects in the case (exposed) group
- 228
- Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
- none
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
- Logistic 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)?
- Yes
- Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
- age, chronic obstructive pulmonary disease, antibiotic exposure
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- decreased
Signature 1
Reviewed Marked as Reviewed by Folakunmi on 2024-3-2
Source: Supplementary figure E8
Description: Relative abundance of individual genera in Endotracheal aspirate (ETA) genera is associated with clinical outcomes and host-response subphenotypes in patients without positive respiratory cultures.
Abundance in Group 1: decreased abundance in Mortality
| NCBI | Quality Control | Links |
|---|---|---|
| Prevotella |
Revision editor(s): Folakunmi
Experiment 2
Reviewed Marked as Reviewed by Folakunmi on 2024-3-4
Differences from previous experiment shown
Subjects
- Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
- Epithelium of oropharynx Oropharyngeal epithelium,Oropharynx epithelial tissue,Oropharynx epithelium,Epithelium of oropharynx,epithelium of oropharynx
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- Acute respiratory failure acute respiratory failure,respiratory failure, acute,Acute respiratory failure
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Hyper-inflammatory subphenotype and mortality
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- VFD (Ventilator free days)
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Clinical outcome stratification by numbers of ventilator-free days (VFDs) at 30 days in patients for whom respiratory specimen cultures were reported as negative (no growth or only normal respiratory flora detected, n=152) as well as those for whom no cultures were obtained (n=76)
Lab analysis
Statistical Analysis
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- decreased
Signature 1
Reviewed Marked as Reviewed by Folakunmi on 2024-3-2
Source: Supplementary figure E8
Description: Relative abundance of individual genera in Endotracheal aspirate (ETA) genera is associated with clinical outcomes and host-response subphenotypes in patients without positive respiratory cultures.
Abundance in Group 1: increased abundance in VFD (Ventilator free days)
| NCBI | Quality Control | Links |
|---|---|---|
| Prevotella | ||
| Streptococcus | ||
| Veillonella | ||
| Rothia | ||
| Granulicatella | ||
| unclassified Pasteurellaceae |
Signature 2
Reviewed Marked as Reviewed by Folakunmi on 2024-3-2
Source: Supplementary figure E8
Description: Relative abundance of individual genera in Endotracheal aspirate (ETA) genera is associated with clinical outcomes and host-response subphenotypes in patients without positive respiratory cultures.
Abundance in Group 1: decreased abundance in VFD (Ventilator free days)
| NCBI | Quality Control | Links |
|---|---|---|
| Staphylococcus |
Experiment 3
Reviewed Marked as Reviewed by Folakunmi on 2024-3-4
Differences from previous experiment shown
Subjects
- Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
- Endothelium of trachea Endothelium of windpipe,Trachea endothelium,Windpipe endothelium,Endothelium of trachea,endothelium of trachea
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- VFD (Ventilator free days) and mortality
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Hyper-inflammatory subphenotype
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- participants were classified into a hyperinflammatory subphenotype of host responses associated with worse outcomes in the pathogen-enriched cluster
- Group 0 sample size Number of subjects in the control (unexposed) group
- 112
- Group 1 sample size Number of subjects in the case (exposed) group
- 51
Lab analysis
Statistical Analysis
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- increased
Signature 1
Reviewed Marked as Reviewed by Folakunmi on 2024-3-1
Source: Figure 4
Description: The relative abundance of individual genera is associated with clinical outcomes and host-response subphenotypes.
Abundance in Group 1: increased abundance in Hyper-inflammatory subphenotype
| NCBI | Quality Control | Links |
|---|---|---|
| Fusobacterium | ||
| unclassified Enterobacteriaceae | ||
| unclassified Pseudomonadaceae | ||
| Staphylococcus |
Revision editor(s): Folakunmi
Experiment 4
Reviewed Marked as Reviewed by Folakunmi on 2024-3-4
Differences from previous experiment shown
Subjects
- Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
- Posterior wall of oropharynx Posterior wall of oropharynx,posterior wall of oropharynx
- Group 0 sample size Number of subjects in the control (unexposed) group
- 96
Lab analysis
Statistical Analysis
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- increased
Signature 1
Reviewed Marked as Reviewed by Folakunmi on 2024-2-29
Source: Figure 4
Description: The relative abundance of individual genera is associated with clinical outcomes and host-response subphenotypes.
Abundance in Group 1: increased abundance in Hyper-inflammatory subphenotype
| NCBI | Quality Control | Links |
|---|---|---|
| Lactobacillus |
Revision editor(s): Folakunmi
Experiment 5
Reviewed Marked as Reviewed by Folakunmi on 2024-3-4
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Hyper-inflammatory subphenotype and ventilation-free days(VFDs)
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Mortality
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- patients stratified on the basis of 30-day mortality [survivors vs. non-survivors]
- Group 0 sample size Number of subjects in the control (unexposed) group
- 92
- Group 1 sample size Number of subjects in the case (exposed) group
- 55
Lab analysis
Statistical Analysis
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- increased
Signature 1
Reviewed Marked as Reviewed by Folakunmi on 2024-2-29
Source: Figure 4
Description: The relative abundance of individual genera is associated with clinical outcomes and host-response subphenotypes.
Abundance in Group 1: increased abundance in Mortality
| NCBI | Quality Control | Links |
|---|---|---|
| Prevotella | ||
| Streptococcus | ||
| Veillonella | ||
| Neisseria |
Revision editor(s): Folakunmi
Experiment 6
Reviewed Marked as Reviewed by Folakunmi on 2024-3-5
Differences from previous experiment shown
Subjects
- Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
- Endothelium of trachea Endothelium of windpipe,Trachea endothelium,Windpipe endothelium,Endothelium of trachea,endothelium of trachea
- Group 0 sample size Number of subjects in the control (unexposed) group
- 111
- Group 1 sample size Number of subjects in the case (exposed) group
- 52
Lab analysis
Statistical Analysis
- Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
- age, antibiotic exposure, chronic obstructive pulmonary disease
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- increased
Signature 1
Reviewed Marked as Reviewed by Folakunmi on 2024-2-29
Source: Figure 4
Description: The relative abundance of individual genera is associated with clinical outcomes and host-response subphenotypes.
Abundance in Group 1: increased abundance in Mortality
| NCBI | Quality Control | Links |
|---|---|---|
| Corynebacterium | ||
| unclassified Eubacteriaceae |
Signature 2
Reviewed Marked as Reviewed by Folakunmi on 2024-2-29
Source: Figure 4
Description: The relative abundance of individual genera is associated with clinical outcomes and host-response subphenotypes.
Abundance in Group 1: decreased abundance in Mortality
| NCBI | Quality Control | Links |
|---|---|---|
| Prevotella | ||
| Haemophilus |
Experiment 7
Reviewed Marked as Reviewed by Folakunmi on 2024-3-5
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Hyper-inflammatory subphenotype and mortality
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- VFD (Ventilator free days)
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- clinical outcome stratifications by the number of days patients were ventilator-free
- Group 0 sample size Number of subjects in the control (unexposed) group
- 103
- Group 1 sample size Number of subjects in the case (exposed) group
- 60
Lab analysis
Statistical Analysis
- Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
- age, chronic obstructive pulmonary disease, antibiotic exposure
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- decreased
Signature 1
Reviewed Marked as Reviewed by Folakunmi on 2024-3-1
Source: Figure 4
Description: The relative abundance of individual genera is associated with clinical outcomes and host-response subphenotypes.
Abundance in Group 1: increased abundance in VFD (Ventilator free days)
| NCBI | Quality Control | Links |
|---|---|---|
| Staphylococcus |
Signature 2
Reviewed Marked as Reviewed by Folakunmi on 2024-3-1
Source: Figure 4
Description: The relative abundance of individual genera is associated with clinical outcomes and host-response subphenotypes.
Abundance in Group 1: decreased abundance in VFD (Ventilator free days)
| NCBI | Quality Control | Links |
|---|---|---|
| Haemophilus | ||
| Rothia | ||
| Gemella | ||
| Streptococcus | ||
| Prevotella |
Experiment 8
Reviewed Marked as Reviewed by Folakunmi on 2024-3-5
Differences from previous experiment shown
Subjects
- Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
- Posterior wall of oropharynx Posterior wall of oropharynx,posterior wall of oropharynx
- Group 0 sample size Number of subjects in the control (unexposed) group
- 106
- Group 1 sample size Number of subjects in the case (exposed) group
- 41
Lab analysis
Statistical Analysis
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- decreased
Signature 1
Reviewed Marked as Reviewed by Folakunmi on 2024-3-5
Source: Figure 4
Description: The relative abundance of individual genera is associated with clinical outcomes and host-response subphenotypes in oral swab samples genera
Abundance in Group 1: decreased abundance in VFD (Ventilator free days)
| NCBI | Quality Control | Links |
|---|---|---|
| Granulicatella | ||
| Neisseria | ||
| Prevotella | ||
| Rothia | ||
| Streptococcus | ||
| Veillonella | ||
| unclassified Pasteurellaceae |
Revision editor(s): Folakunmi
Experiment 9
Reviewed Marked as Reviewed by Folakunmi on 2024-3-5
Differences from previous experiment shown
Subjects
- Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
- Endothelium of trachea Endothelium of windpipe,Trachea endothelium,Windpipe endothelium,Endothelium of trachea,endothelium of trachea
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Hyper-inflammatory subphenotype and ventilation-free days(VFDs)
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Mortality
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- patients stratified on the basis of 30-day mortality [survivors vs. non-survivors] , for whom respiratory specimen cultures were reported as negative (no growth or only normal respiratory flora detected, n=152) as well as those for whom no cultures were obtained (n=76)
- Group 0 sample size Number of subjects in the control (unexposed) group
- 228
- Group 1 sample size Number of subjects in the case (exposed) group
- 228
- Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
- 30 days
Lab analysis
Statistical Analysis
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- decreased
Signature 1
Reviewed Marked as Reviewed by Folakunmi on 2024-3-5
Source: Supplementary figure E8
Description: Relative abundance of individual genera in Endotracheal aspirate (ETA) genera is associated with clinical outcomes and host-response subphenotypes in patients without positive respiratory cultures.
Abundance in Group 1: decreased abundance in Mortality
| NCBI | Quality Control | Links |
|---|---|---|
| Prevotella |
Revision editor(s): Folakunmi
Experiment 10
Reviewed Marked as Reviewed by Folakunmi on 2024-3-5
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Hyper-inflammatory subphenotype and mortality
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- VFD (Ventilator free days)
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- clinical outcome stratifications by the number of days patients were ventilator-free for whom respiratory specimen cultures were reported as negative (no growth or only normal respiratory flora detected, n=152) as well as those for whom no cultures were obtained (n=76)
- Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
- none
Lab analysis
Statistical Analysis
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- decreased
Signature 1
Reviewed Marked as Reviewed by Folakunmi on 2024-3-2
Source: Supplementary figure E8
Description: Relative abundance of individual genera in Endotracheal aspirate (ETA) genera is associated with clinical outcomes and host-response subphenotypes in patients without positive respiratory cultures.
Abundance in Group 1: decreased abundance in VFD (Ventilator free days)
| NCBI | Quality Control | Links |
|---|---|---|
| Haemophilus | ||
| Prevotella |
Revision editor(s): Folakunmi
Experiment 11
Reviewed Marked as Reviewed by Folakunmi on 2024-3-5
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- VFD (Ventilator free days) and mortality
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Hyper-inflammatory subphenotype
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- participants who were classified into a hyperinflammatory subphenotype of host responses, for whom respiratory specimen cultures were reported as negative (no growth or only normal respiratory flora detected, n=152) as well as those for whom no cultures were obtained (n=76)
Lab analysis
Statistical Analysis
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- increased
Experiment 12
Reviewed Marked as Reviewed by Folakunmi on 2024-3-5
Differences from previous experiment shown
Subjects
- Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
- Epithelium of oropharynx Oropharyngeal epithelium,Oropharynx epithelial tissue,Oropharynx epithelium,Epithelium of oropharynx,epithelium of oropharynx
Lab analysis
Statistical Analysis
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- increased
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