Lung Microbiota and Metabolites Collectively Associate with Clinical Outcomes in Milder Stage Chronic Obstructive Pulmonary Disease.

TitleLung Microbiota and Metabolites Collectively Associate with Clinical Outcomes in Milder Stage Chronic Obstructive Pulmonary Disease.
Publication TypePublication
Year2022
AuthorsMadapoosi SS, Cruickshank-Quinn C, Opron K, Erb-Downward JR, Begley LA, Li G, Barjaktarevic I, R Barr G, Comellas AP, Couper DJ, Cooper CB, Freeman CM, Han MK, Kaner RJ, Labaki W, Martinez FJ, Ortega VE, Peters SP, Paine R, Woodruff P, Curtis JL, Huffnagle GB, Stringer KA, Bowler RP, Esther CR, Reisdorph N, Huang YJ
Corporate AuthorsSPIROMICS Research Group
JournalAm J Respir Crit Care Med
Volume206
Issue4
Pagination427-439
Date Published2022 08 15
ISSN1535-4970
KeywordsAdenosine, Humans, Lung, Microbiota, Pulmonary Disease, Chronic Obstructive, RNA, Ribosomal, 16S
Abstract

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. Identify components of the lung microbiome and metabolome collectively associated with clinical markers in milder stage COPD. 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 ) bacterial 16S rRNA gene sequencing; ) untargeted metabolomics of the hydrophobic fraction, largely comprising lipids; and ) 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). The majority of clinical measures associated with the lung microbiome and metabolome collectively in overall models (classification accuracies, >50%,  < 0.05 vs. chance). Lower lung function, COPD diagnosis, and greater symptoms associated positively with , , and , together with compounds from several classes (glycosphingolipids, glycerophospholipids, polyamines and xanthine, an adenosine metabolite). In contrast, several members, together with adenosine, 5'-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 ( < 0.05). Components of the lung microbiome and metabolome in combination relate to outcome measures in milder COPD, highlighting their potential collaborative roles in disease pathogenesis.

DOI10.1164/rccm.202110-2241OC
Alternate JournalAm J Respir Crit Care Med
PubMed ID35536732
Grant ListR01AI129958 / / National Institute of Allergy and Infectious Diseases /
R01HL121774 / HL / NHLBI NIH HHS / United States
R01HL121774-S1 / HL / NHLBI NIH HHS / United States
U01 HL137880 / HL / NHLBI NIH HHS / United States
U24 HL141762 / HL / NHLBI NIH HHS / United States
HHSN268200900013C / HL / NHLBI NIH HHS / United States
HHSN268200900014C / HL / NHLBI NIH HHS / United States
HHSN268200900015C / HL / NHLBI NIH HHS / United States
HHSN268200900016C / HL / NHLBI NIH HHS / United States
HHSN268200900017C / HL / NHLBI NIH HHS / United States
HHSN268200900018C / HL / NHLBI NIH HHS / United States
HHSN268200900019C / HL / NHLBI NIH HHS / United States
HHSN268200900020C / HL / NHLBI NIH HHS / United States
MS#: 
MS209
Manuscript Full Title: 
Lung Microbiota and Metabolites Collectively Associate with Clinical Outcomes in Milder Stage Chronic Obstructive Pulmonary Disease.
Manuscript Lead/Corresponding Author Affiliation: 
Clinical Center: Michigan (University of Michigan)
ECI: 
Manuscript Status: 
Published and Public