Taxonomic and functional dynamics of lung microbiome in cystic fibrosis patients chronically infected with Pseudomonas aeruginosa

Background: Although the cystic fibrosis (CF) lung microbiome has been taxonomically defined, little is still known about the overall gene content and functional profiles of the resident microbiome and how it changes in relation with patient9s disease status. The aim of this study was to investigate the taxonomic and functional temporal dynamics of airways microbiome in CF patients with chronic Pseudomonas aeruginosa infection. A shotgun metagenomic approach was used, to target the entire genomic repertoire of the microbial community and allow strain-level profiling. Results: A cohort of 22 patients with moderate-severe lung disease carrying the ΔF508 mutation was enrolled and followed over 15 months. The taxonomic composition, metabolic repertoire and antibiotic resistance gene content of lung microbiome was investigated by time-resolved shotgun metagenomics. A high inter-patient taxonomic heterogeneity was found with short-term compositional changes during period of exacerbation and following antibiotic treatment. Each patient represented a unique environment showing distinct communities at the taxonomic level and a high patient-specific colonization by both main and emerging CF pathogens. The extraordinary resilience of the CF microbiome was found even from a functional perspective. All samples showed a core set of antibiotic resistance genes with a limited influence of antibiotic intake. Conclusions: The main outcomes from this study indicate a patient-specific temporal dynamic of the microbiome and a high functional resilience following exacerbation and antibiotic treatment.