Respiratory Tract Dysbiosis Is Associated with Worse Outcomes in Mechanically Ventilated Patients

From BugSigDB
Reviewed Marked as Reviewed by Chloe on 2023-3-20
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


incomplete

Curated date: 2023/03/12

Curator: Dherahrose

Revision editor(s): Dherahrose, Chloe, Atrayees

Subjects

Location of subjects
United States of America
Host species Species from which microbiome was sampled (if applicable)
Homo sapiens


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
acute respiratory distress syndrome
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Respiratory tract dysbiosis
Group 0 sample size Number of subjects in the control (unexposed) group
300
Group 1 sample size Number of subjects in the case (exposed) group
301
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
30days

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
PERMANOVA
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
Matched on Factors on which subjects have been matched on in a case-control study
age, sex
Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
age, antibiotic exposure

Alpha Diversity

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

Signature 1

incomplete

Curated date: 2023/03/12

Curator: Dherahrose

Revision editor(s): Dherahrose, Chloe

Source: Figure 1

Description: Dirichlet-multinomial-model clustering of endotracheal aspirate communities reveals a distinct cluster marked by pathogen abundance and low alpha diversity.

Abundance in Group 1: increased abundance in acute respiratory distress syndrome

NCBI Quality ControlLinks
Pseudomonadaceae
Staphylococcus
Stenotrophomonas
Streptococcus

Revision editor(s): Dherahrose, Chloe

Signature 2

incomplete

Curated date: 2023/03/12

Curator: Dherahrose

Revision editor(s): Dherahrose, Chloe

Source: Figure 1

Description: Dirichlet-multinomial-model clustering of endotracheal aspirate communities reveals a distinct cluster marked by pathogen abundance and low alpha diversity.

Abundance in Group 1: decreased abundance in acute respiratory distress syndrome

NCBI Quality ControlLinks
Enterobacter cloacae
Gemella
Haemophilus

Revision editor(s): Dherahrose, Chloe

Experiment 2


Needs review

Curated date: 2023/06/20

Curator: Atrayees

Revision editor(s): Atrayees

Differences from previous experiment shown

Subjects

Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
Oropharynx , Lower respiratory tract , Upper respiratory tract Mesopharynx,Oral part of pharynx,Pars oralis pharyngis,Oropharynx,Lower respiratory system,Lower respiratory tract,Upper respiratory tract
Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
acute respiratory failure acute respiratory failure,respiratory failure, acute
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Survivors
Group 1 name Corresponds to the case (exposed) group for case-control studies
Non-survivors
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Non-survivors
Group 0 sample size Number of subjects in the control (unexposed) group
Not specified
Group 1 sample size Number of subjects in the case (exposed) group
Not specified
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

Statistical test
Not specified
Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
Not specified
Matched on Factors on which subjects have been matched on in a case-control study
Not specified
Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
Not specified

Alpha Diversity

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

Signature 1

Needs review

Curated date: 2023/06/20

Curator: Atrayees

Revision editor(s): Atrayees

Source: Figure E9

Description: Differentially abundant genera in the two groups

Abundance in Group 1: increased abundance in Non-survivors

NCBI Quality ControlLinks
Staphylococcus
Escherichia
Enterobacteriaceae
Pseudomonadaceae

Revision editor(s): Atrayees

Signature 2

Needs review

Curated date: 2023/06/20

Curator: Atrayees

Revision editor(s): Atrayees

Source: Figure E9

Description: Differentially abundant genera in the two groups

Abundance in Group 1: decreased abundance in Non-survivors

NCBI Quality ControlLinks
Prevotella

Revision editor(s): Atrayees

Experiment 3


Needs review

Curated date: 2023/06/20

Curator: Atrayees

Revision editor(s): Atrayees

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Patients with fewer VFDs
Group 1 name Corresponds to the case (exposed) group for case-control studies
Patients with more VFDs
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patients with more VFDs (Ventilator-free days)

Lab analysis

Statistical Analysis

Statistical test
Kruskall-Wallis

Alpha Diversity

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

Signature 1

Needs review

Curated date: 2023/06/20

Curator: Atrayees

Revision editor(s): Atrayees

Source: Figure E10

Description: Differentially abundant genera by VFD tertiles

Abundance in Group 1: increased abundance in Patients with more VFDs

NCBI Quality ControlLinks
Streptococcus

Revision editor(s): Atrayees

Signature 2

Needs review

Curated date: 2023/06/20

Curator: Atrayees

Revision editor(s): Atrayees

Source: Figure E10

Description: Differentially abundant genera by VFD tertiles

Abundance in Group 1: decreased abundance in Patients with more VFDs

NCBI Quality ControlLinks
Staphylococcus
Escherichia

Revision editor(s): Atrayees

Experiment 4


Needs review

Curated date: 2023/06/20

Curator: Atrayees

Revision editor(s): Atrayees

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Survivors
Group 1 name Corresponds to the case (exposed) group for case-control studies
Non-survivors
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Non-survivors

Lab analysis

Statistical Analysis

Statistical test
Not specified

Alpha Diversity

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

Signature 1

Needs review

Curated date: 2023/06/20

Curator: Atrayees

Revision editor(s): Atrayees

Source: Figure E11

Description: Differentially abundant genera in the two groups

Abundance in Group 1: decreased abundance in Non-survivors

NCBI Quality ControlLinks
Prevotella

Revision editor(s): Atrayees

Experiment 5


Needs review

Curated date: 2023/06/20

Curator: Atrayees

Revision editor(s): Atrayees

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Patients with fewer VFDs
Group 1 name Corresponds to the case (exposed) group for case-control studies
Patients with more VFDs
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patients with more VFDs

Lab analysis

Statistical Analysis

Statistical test
Kruskall-Wallis

Alpha Diversity

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

Signature 1

Needs review

Curated date: 2023/06/20

Curator: Atrayees

Revision editor(s): Atrayees

Source: Figure E12

Description: Differentially abundant genera by VFD tertiles

Abundance in Group 1: increased abundance in Patients with more VFDs

NCBI Quality ControlLinks
Prevotella
Rothia
Streptococcus
Neisseria
Veillonella
Granulicatella
Pasteurellaceae

Revision editor(s): Atrayees

Signature 2

Needs review

Curated date: 2023/06/20

Curator: Atrayees

Revision editor(s): Atrayees

Source: Figure E12

Description: Differentially abundant genera by VFD tertiles

Abundance in Group 1: decreased abundance in Patients with more VFDs

NCBI Quality ControlLinks
Enterobacteriaceae
Pseudomonadaceae

Revision editor(s): Atrayees

Experiment 6


Needs review

Curated date: 2023/06/23

Curator: Atrayees

Revision editor(s): Atrayees

Differences from previous experiment shown

Subjects

Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
Upper respiratory tract , Lower respiratory tract Upper respiratory tract,Lower respiratory system,Lower respiratory tract
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Hyper-inflammatory subphenotype
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
Not specified

Lab analysis

Statistical Analysis

Statistical test
Not specified
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)?
Not specified


Signature 1

Needs review

Curated date: 2023/06/23

Curator: Atrayees

Revision editor(s): Atrayees

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 ControlLinks
Prevotella

Revision editor(s): Atrayees

Signature 2

Needs review

Curated date: 2023/06/23

Curator: Atrayees

Revision editor(s): Atrayees

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 ControlLinks
Fusobacterium
Staphylococcus
unclassified Enterobacteriaceae
unclassified Pseudomonadaceae

Revision editor(s): Atrayees

Experiment 7


Needs review

Curated date: 2023/06/23

Curator: Atrayees

Revision editor(s): Atrayees

Differences from previous experiment shown

Subjects

Group 1 name Corresponds to the case (exposed) group for case-control studies
VFD (Ventilator free days)

Lab analysis

Statistical Analysis

Signature 1

Needs review

Curated date: 2023/06/23

Curator: Atrayees

Revision editor(s): Atrayees

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 ControlLinks
Prevotella
Haemophilus
Streptococcus

Revision editor(s): Atrayees

Signature 2

Needs review

Curated date: 2023/06/23

Curator: Atrayees

Revision editor(s): Atrayees

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 ControlLinks
Fusobacterium
unclassified Enterobacteriaceae
unclassified Pseudomonadaceae

Revision editor(s): Atrayees