Abstract
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.
Highlights
We describe the bacterial community structure of sputum samples from 269 cystic fibrosis patients across a broad range of age, disease stage, clinical status and treatment using a culture-independent method
This is the largest cohort of Cystic fibrosis (CF) patients spanning both adult and pediatric populations for whom sputum has been analysed by 16S rRNA gene sequencing yet published, and includes a large number of patients younger than 18 years of age
A small number of taxa accounted for the bulk of bacterial sequences present in any sample, and approximately half of all patients had a bacterial community dominated by a single genus
Summary
The size of the core microbiota of adult and pediatric samples, arbitrarily defined in our study as genera with a relative abundance of ≥1% of sequence in ≥50% of samples, were similar in both groups (Fig. 1A, Table 2). 18+ (median, range) number of samples in which the genus was dominant divided by the total number of samples in which it was present with >1% relative abundance), Pseudomonas and Burkholderia, when dominant, accounted for a larger proportion of the community than Streptococcus in Streptococcus-dominant samples (72.8%, 78.2% and 47.1% of sequence in adult samples respectively, P < 0.0005).
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