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

Study information

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

study design

prospective cohort

Citation

PMID PubMed identifier for scientific articles.

32717152

DOI Digital object identifier for electronic documents.

10.1164/rccm.201912-2441OC

URI Uniform resource identifier for web resources.

https://pubmed.ncbi.nlm.nih.gov/32717152/

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

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

Edit History Delete Duplicate this Experiment Add a new Signature

incomplete

Curated date: 2023/03/12

Curator: Dherahrose

Revision editor(s): Dherahrose, Chloe

Subjects

Location of subjects: India

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): 0.001
MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?: No

Matched on Factors on which subjects have been matched on in a case-control study: age, sex

Alpha Diversity

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

Signature 1

Edit History Delete

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	Links
Pseudomonadaceae
Staphylococcus
Stenotrophomonas ⚠
Streptococcus

Revision editor(s): Dherahrose, Chloe

Signature 2

Edit History Delete

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	Links
Enterobacter cloacae ⚠
Gemella
Haemophilus

Revision editor(s): Dherahrose, Chloe