Lung microbiota across age and disease stage in cystic fibrosis (original) (raw)

Understanding the significance of bacterial species that colonize and persist in cystic fibrosis (CF) airways requires a detailed examination of bacterial community structure across a broad range of age and disease stage. We used 16S ribosomal RNA sequencing to characterize the lung microbiota in 269 CF patients spanning a 60 year age range, including 76 pediatric samples from patients of age 4-17, and a broad cross-section of disease status to identify features of bacterial community structure and their relationship to disease stage and age. The CF lung microbiota shows significant inter-individual variability in community structure, composition and diversity. The core microbiota consists of five genera-Streptococcus, Prevotella, Rothia, Veillonella and Actinomyces. CF-associated pathogens such as Pseudomonas, Burkholderia, Stenotrophomonas and Achromobacter are less prevalent than core genera, but have a strong tendency to dominate the bacterial community when present. Community diversity and lung function are greatest in patients less than 10 years of age and lower in older age groups, plateauing at approximately age 25. Lower community diversity correlates with worse lung function in a multivariate regression model. Infection by Pseudomonas correlates with age-associated trends in community diversity and lung function. Cystic fibrosis (CF) is characterized by recurrent airway infection, inflammation and progressive decline in lung function. Infection with key organisms such as Pseudomonas aeruginosa and Burkholderia cepacia complex (Bcc) has been associated with the frequent exacerbations of airway dysfunction and progressive functional decline that are the hallmarks of the disease 1-3. Over the last decade, cross-sectional and longitudinal studies of bacterial taxa using culture-independent microbial detection methods such as terminal restriction fragment length polymorphism (T-RFLP) and 16S rRNA gene sequencing, have identified polymicrobial communities in the airways of CF patients that exceed the complexity captured by traditional culture 4-13. Significant heterogeneity in bacterial community composition has been demonstrated within groups of clinically similar patients 5-7. Although the abundance of individual taxa (such as Gemella spp. and the Streptococcus anginosus group), ecological diversity, and community stability are potentially associated with disease status 8,10,14 , no single static or dynamic metric or bacterial taxon has emerged that consistently explains the heterogeneity of disease within otherwise similar hosts. Culture-based methods have demonstrated the clinical significance of infection with pathogens such as P. aeruginosa. Molecular methods have demonstrated that not only their presence or absence, but also