The Evolving Cystic Fibrosis Microbiome: A Comparative Cohort Study Spanning 16 Years

Rationale: The cystic fibrosis (CF) airways are infected with a diverse polymicrobial community. Objectives: Understanding how changes in the CF microbiome have occurred over time, similar to the observed changes in the prevalence of cultured pathogens, is key in understanding the microbiome's role in disease. Methods: Drawing from a prospectively collected and maintained sputum biobank, we identified 45 patients with sputum samples collected between the ages of 18 and 21 years in three successive cohorts of adults transitioning to our CF clinic: A (1997-2000), B (2004-2007), and C (2010-2013). Patient demographics, clinical status, and medications were collected from detailed chart review. Microbial communities were assessed by Ilumina MiSeq sequencing of the variable 3 (V3) region of the 16S rDNA. Results: The three cohorts were similar with respect to baseline demographics. There was a trend toward improved health and use of disease-modifying therapies in each successive cohort. Shannon diversity increased in the most recent cohort, suggesting an increase in the diversity of organisms between cohorts. Furthermore, the proportion of samples with Pseudomonas-dominated communities decreased over time, whereas Streptococcus increased. Although beta-diversity was associated with transition cohort, the greatest predictor of diversity remained lung function. Furthermore, core microbiome constituents were preserved across cohorts. Conclusions: Modest changes in the composition and structure of the microbiome of three successive cohorts of young adults with CF were observed, occurring in parallel with successive improvements in clinical status. Importantly, however, the core microbiome constituents were preserved across cohorts.