Airway Microbiome Dynamics in Exacerbations of Chronic Obstructive Pulmonary Disease

Abstract

Specific bacterial species are implicated in the pathogenesis of exacerbations of chronic obstructive pulmonary disease (COPD).However, recent studies of clinically stable COPD patients have demonstrated a greater diversity of airway microbiota, whose role in acute exacerbations is unclear. In this study, temporal changes in the airway microbiome before, at the onset of, and after an acute exacerbation were examined in 60 sputum samples collected from subjects enrolled in a longitudinal study of bacterial infection in COPD. Microbiome composition and predicted functions were examined using 16S rRNA-based culture-independent profiling methods. Shifts in the abundance (>2-fold, P < 0.05) of many taxa at exacerbation and after treatment were observed. Microbiota members that were increased at exacerbation were primarily of the Proteobacteria phylum, including nontypical COPD pathogens. Changes in the bacterial composition after treatment for an exacerbation differed significantly among the therapy regimens clinically prescribed (antibiotics only, oral corticosteroids only, or both). Treatment with antibiotics alone primarily decreased the abundance of Proteobacteria, with the prolonged suppression of some microbiota members being observed. In contrast, treatment with corticosteroids alone led to enrichment for Proteobacteria and members of other phyla. Predicted metagenomes of particular microbiota members involved in these compositional shifts indicated exacerbation-associated loss of functions involved in the synthesis of antimicrobial and anti-inflammatory products, alongside enrichment in functions related to pathogen-elicited inflammation. These trends reversed upon clinical recovery. Further larger studies will be necessary to determine whether specific compositional or functional changes detected in the airway microbiome could be useful indicators of exacerbation development or outcome.A cute exacerbations of chronic obstructive pulmonary disease (AECOPD) are a major source of morbidity, characterized by worsening of respiratory symptoms from the baseline normal variation that require new treatment (http://www.goldcopd.org/). Culture-based evaluations have implicated bacteria in ϳ50% of exacerbations (1). While acquisition of new strains of Haemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis, and Pseudomonas aeruginosa is associated with exacerbations (2, 3), these represent relatively few species compared to the overall diversity of airway microbiota recently described in COPD (4-7).Detection of bacteria in most prior studies was limited by the use of culture-based methods (8, 9). Application of more sensitive molecular tools has consistently shown a greater diversity of airway microbiota in COPD, despite differences in specimens and platforms across studies (4-7, 10). With increasing appreciation of the fact that the microbial microenvironment can modify the behavior of primary pathogens (11,12), this invites speculation that other microbiota members may contribute to the pathogenesis o...

Lung microbiome dynamics in COPD exacerbations

“…In agreement with HUANG et al [8], we found a decreased microbial α diversity with an increase of Proteobacteria over Firmicutes in subjects treated with corticosteroids alone (figure 4). At the genus level, this corresponded to a decrease of Streptococcus and an increase of Haemophilus and Moraxella.…”

“…The genera Streptococcus (prevalence 95.0%), Haemophilus (94.7%), Rothia (94.1%), Veillonella (93.2%) and Prevotella (90.3%) were highly prevalent across all visits (table 3). There was a significantly greater inter-subject variation in microbiome community at the same visit (weighted UniFrac±SD 0.387±0.186) compared with temporal variation within each subject (weighted UniFrac±SD 0.272±0.181, p=2.2e−16 using t-test), suggesting that for our cohort the lung microbiome was relatively stable over time [8].…”

“…Since antibiotics and steroids can alter the lung microbiome in COPD patients [8], we investigated the changes in the microbiome resulting from these treatments. In agreement with HUANG et al [8], we found a decreased microbial α diversity with an increase of Proteobacteria over Firmicutes in subjects treated with corticosteroids alone (figure 4).…”

“…Studies using culture-independent techniques such as PCR amplification and sequencing of the 16S ribosomal (r)RNA gene have characterised a distinct bacterial community in the airway of COPD patients compared to healthy subjects and suggest that changes in the lung microbiota could be associated with enhanced airway inflammation and disease progression [8][9][10][11]. However, most lung microbiome studies to date have involved relatively small cohorts of subjects with limited longitudinal sampling and concurrent clinical information.…”

Le microbiome pulmonaire en 2015

“…De nombreuses pistes ont été décrites pour expliquer comment l'exposition tabagique détruit les défenses pulmonaires de l'hôte via la suppression de la production de peptides antimicrobiens, la destruction de la barrière épithéliale et la colonisation des voies aériennes inférieures par un certain nombre d'agents microbiologiques [25,30,31] [33]. Le microbiote est également modifié par l'antibiothérapie et la corticothérapie [24]. Il est également différent chez les patients atteints de mucoviscidose.…”