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

被引:271
作者
Fodor, Anthony A. [1 ]
Klem, Erich R. [2 ]
Gilpin, Deirdre F. [3 ,4 ]
Elborn, J. Stuart [3 ,5 ]
Boucher, Richard C. [2 ]
Tunney, Michael M. [3 ,4 ]
Wolfgang, Matthew C. [2 ,6 ]
机构
[1] Univ N Carolina, Dept Bioinformat & Genom, Charlotte, NC 28223 USA
[2] Univ N Carolina, Cyst Fibrosis Pulm Res & Treatment Ctr, Chapel Hill, NC USA
[3] Queens Univ Belfast, CF & Airway Microbiol Res Grp, Belfast, Antrim, North Ireland
[4] Queens Univ Belfast, Sch Pharm, Belfast, Antrim, North Ireland
[5] Queens Univ Belfast, Sch Med Dent & Biomed Sci, Ctr Infect & Immun, Belfast, Antrim, North Ireland
[6] Univ N Carolina, Dept Microbiol & Immunol, Chapel Hill, NC USA
来源
PLOS ONE | 2012年 / 7卷 / 09期
基金
美国国家卫生研究院; 英国医学研究理事会;
关键词
MUCOID PSEUDOMONAS-AERUGINOSA; LUNG-FUNCTION DECLINE; PULMONARY EXACERBATIONS; BACTERIAL COMMUNITIES; ANAEROBIC-BACTERIA; RESPIRATORY-TRACT; UNITED-STATES; SPUTUM; PREVOTELLA; DIVERSITY;
D O I
10.1371/journal.pone.0045001
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
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页数:15
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