Journal article
Lung Microbiota and Metabolites Collectively Associate with Clinical Outcomes in Milder Stage Chronic Obstructive Pulmonary Disease
American journal of respiratory and critical care medicine, Vol.206(4), pp.427-439
08/15/2022
DOI: 10.1164/rccm.202110-2241OC
PMCID: PMC11418810
PMID: 35536732
Abstract
Rationale: Chronic obstructive pulmonary disease (COPD) is variable in its development. Lung microbiota and metabolites collectively may impact COPD pathophysiology, but relationships to clinical outcomes in milder disease are unclear.
Objectives: Identify components of the lung microbiome and metabolome collectively associated with clinical markers in milder stage COPD.
Methods: We analyzed paired microbiome and metabolomic data previously characterized from bronchoalveolar lavage fluid in 137 participants in the SPIROMICS (Subpopulations and Intermediate Outcome Measures in COPD Study), or (GOLD [Global Initiative for Chronic Obstructive Lung Disease Stage 0-2). Datasets used included 1) bacterial 16S rRNA gene sequencing; 2) untargeted metabolomics of the hydrophobic fraction, largely comprising lipids; and 3) targeted metabolomics for a panel of hydrophilic compounds previously implicated in mucoinflammation. We applied an integrative approach to select features and model 14 individual clinical variables representative of known associations with COPD trajectory (lung function, symptoms, and exacerbations).
Measurements and Main Results: The majority of clinical measures associated with the lung microbiome and metabolome collectively in overall models (classification accuracies, >50%, P < 0.05 vs. chance). Lower lung function, COPD diagnosis, and greater symptoms associated positively with Streptococcus, Neisseria, and Veillonella, together with compounds from several classes (glycosphingolipids, glycerophospholipids, polyamines and xanthine, an adenosine metabolite). In contrast, several Prevotella members, together with adenosine, 59-methylthioadenosine, sialic acid, tyrosine, and glutathione, associated with better lung function, absence of COPD, or less symptoms. Significant correlations were observed between specific metabolites and bacteria (P-adj < 0.05).
Conclusions: Components of the lung microbiome and metabolome in combination relate to outcome measures in milder COPD, highlighting their potential collaborative roles in disease pathogenesis.
Details
- Title: Subtitle
- Lung Microbiota and Metabolites Collectively Associate with Clinical Outcomes in Milder Stage Chronic Obstructive Pulmonary Disease
- Creators
- Siddharth S. Madapoosi - University of Michigan–Ann ArborCharmion Cruickshank-Quinn - University of Colorado Anschutz Medical CampusKristopher Opron - University of Michigan–Ann ArborJohn R. Erb-Downward - University of Michigan–Ann ArborLesa A. Begley - University of Michigan–Ann ArborGen Li - University of Michigan–Ann ArborIgor Barjaktarevic - University of California SystemDavid J. Couper - University of North Carolina at Chapel HillChristopher B. Cooper - Ronald Reagan UCLA Medical CenterChristine M. Freeman - University of Michigan–Ann ArborMeiLan K. Han - University of MichiganRobert J. Kaner - Cornell UniversityWassim Labaki - University of MichiganFernando J. Martinez - Cornell UniversityVictor E. Ortega - Mayo Clinic in FloridaStephen P. Peters - Wake Forest UniversityRobert Paine - University of UtahPrescott Woodruff - University of California, San FranciscoJeffrey L. Curtis - University of Michigan–Ann ArborGary B. Huffnagle - University of Michigan–Ann ArborKathleen A. Stringer - University of MichiganRussell P. Bowler - National Jewish HealthCharles R Esther Jr - Univ N Carolina, Div Pediat Pulmonol, Chapel Hill, NC 27515 USANichole Reisdorph - University of MontanaYvonne J. Huang - University of Michigan–Ann ArborSubPopulations and InteRmediate Outcome Measures In COPD Study (SPIROMICS) Research Group
- Contributors
- Eric A Hoffman (Contributor) - University of Iowa, Radiology
- Resource Type
- Journal article
- Publication Details
- American journal of respiratory and critical care medicine, Vol.206(4), pp.427-439
- DOI
- 10.1164/rccm.202110-2241OC
- PMID
- 35536732
- PMCID
- PMC11418810
- NLM abbreviation
- Am J Respir Crit Care Med
- ISSN
- 1073-449X
- eISSN
- 1535-4970
- Publisher
- Amer Thoracic Soc
- Number of pages
- 13
- Grant note
- R01HL121774-S1; R01AI129958; R01HL121774 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA U01 HL137880; U24 HL141762; HHSN268200900013C; HHSN268200900014C; HHSN268200900015C; HHSN268200900016C; HHSN268200900017C; HHSN268200900018C; HHSN268200900019C; HHSN268200900020C / NHLBI; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI)
- Language
- English
- Date published
- 08/15/2022
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Radiology; Internal Medicine
- Record Identifier
- 9984318718202771
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