High Individuality of Respiratory Bacterial Communities in a Large Cohort of Adult Cystic Fibrosis Patients under Continuous Antibiotic Treatment

BACKGROUND: Routine clinical diagnostics of CF patients focus only on a restricted set of well-known pathogenic species. Recent molecular studies suggest that infections could be polymicrobial with many bacteria not detected by culture-based diagnostics. METHODOLOGY AND PRINCIPAL FINDINGS: A large cohort of 56 adults with continuous antibiotic treatment was studied and different microbial diagnostic methods were compared, including culture-independent and culture-based bacterial diagnostics. A total of 72 sputum samples including longitudinal observations was analysed by 16S rRNA gene sequence comparison. Prevalence of known pathogens was highly similar among all methods but the vast spectrum of bacteria associated with CF was only revealed by culture-independent techniques. The sequence comparison enabled confident determination of the bacterial community composition and revealed a high diversity and individuality in the communities across the cohort. Results of microbiological analyses were further compared with individual host factors, such as age, lung function and CFTR genotype. No statistical relationship between these factors and the diversity of the entire community or single bacterial species could be identified. However, patients with non-ΔF508 mutations in the CFTR gene often had low abundances of Pseudomonas aeruginosa. Persistence of specific bacteria in some communities was demonstrated by longitudinal analyses of 13 patients indicating a potential clinical relevance of anaerobic bacteria, such as Fusobacterium nucleatum and Streptococcus millerii. CONCLUSIONS: The high individuality in community composition and the lack of correlation to clinical host factors might be due to the continuous treatment with antibiotics. Since this is current practice for adult CF patients, the life-long history of the patient and the varying selection pressure on the related microbial communities should be a focus of future studies and its relation to disease progression. These studies should be substantially larger, providing more molecular information on the microbial communities complemented by detailed genetic assessment of the host.