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The Adult Cystic Fibrosis Airway Microbiota Is Stable over Time and Infection Type, and Highly Resilient to Antibiotic Treatment of Exacerbations

Title: The Adult Cystic Fibrosis Airway Microbiota Is Stable over Time and Infection Type, and Highly Resilient to Antibiotic Treatment of Exacerbations
Authors: Fodor, AA
Klem, ER
Gilpin, DF
Elborn, JS
Boucher, RC
Tunney, MM
Wolfgang, MC
Item Type: Journal Article
Abstract: Cystic fibrosis (CF) is characterized by defective mucociliary clearance and chronic airway infection by a complex microbiota. Infection, persistent inflammation and periodic episodes of acute pulmonary exacerbation contribute to an irreversible decline in CF lung function. While the factors leading to acute exacerbations are poorly understood, antibiotic treatment can temporarily resolve pulmonary symptoms and partially restore lung function. Previous studies indicated that exacerbations may be associated with changes in microbial densities and the acquisition of new microbial species. Given the complexity of the CF microbiota, we applied massively parallel pyrosequencing to identify changes in airway microbial community structure in 23 adult CF patients during acute pulmonary exacerbation, after antibiotic treatment and during periods of stable disease. Over 350,000 sequences were generated, representing nearly 170 distinct microbial taxa. Approximately 60% of sequences obtained were from the recognized CF pathogens Pseudomonas and Burkholderia, which were detected in largely non-overlapping patient subsets. In contrast, other taxa including Prevotella, Streptococcus, Rothia and Veillonella were abundant in nearly all patient samples. Although antibiotic treatment was associated with a small decrease in species richness, there was minimal change in overall microbial community structure. Furthermore, microbial community composition was highly similar in patients during an exacerbation and when clinically stable, suggesting that exacerbations may represent intrapulmonary spread of infection rather than a change in microbial community composition. Mouthwash samples, obtained from a subset of patients, showed a nearly identical distribution of taxa as expectorated sputum, indicating that aspiration may contribute to colonization of the lower airways. Finally, we observed a strong correlation between low species richness and poor lung function. Taken together, these results indicate that the adult CF lung microbiome is largely stable through periods of exacerbation and antibiotic treatment and that short-term compositional changes in the airway microbiota do not account for CF pulmonary exacerbations.
Issue Date: 26-Sep-2012
Date of Acceptance: 11-Aug-2012
URI: http://hdl.handle.net/10044/1/41963
DOI: http://dx.doi.org/10.1371/journal.pone.0045001
ISSN: 1932-6203
Publisher: Public Library of Science
Journal / Book Title: PLOS One
Volume: 7
Issue: 9
Copyright Statement: © Fodor et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Keywords: Adult
Anti-Bacterial Agents
Chronic Disease
Cystic Fibrosis
DNA, Bacterial
Disease Progression
Drug Resistance, Multiple, Bacterial
Gram-Negative Bacteria
Gram-Positive Bacteria
High-Throughput Nucleotide Sequencing
Humans
Metagenome
Phylogeny
Respiratory System
Sputum
General Science & Technology
MD Multidisciplinary
Publication Status: Published
Article Number: e45001
Appears in Collections:National Heart and Lung Institute
Faculty of Medicine



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