37 The microbial metagenome of cystic fibrosis lower airways

Abstract

The use of culture-independent microbiome analysis is expanding our view of respiratory tract infection in Cystic fibrosis (CF). The lower airways of people with CF are colonized with polymicrobial communities of bacteria, viruses, fungi and molds. We investigated the microbial metagenome in 20 exocrine pancreatic insufficient and 10 exocrine pancreatic sufficient CF patients. One to five sputum samples were collected from each patient over a 2-year period. The isolated DNA was sequenced by random whole genome sequencing. The reads were aligned to the human, bacterial, virus, fungi and molds reference genomes. Sequences were normalized by GC content and length reference genome. Analysis of temporal series of specimens indicate that each patient carries a specific signature of microbes in his airways unless drastic interventions were undertaken to eradicate unpleasant pathogens such as Burkholderia spp. The spectrum of bacterial species ranged from metagenomes indistinguishable from a healthy non-CF control to metagenomes dominated by the typical CF pathogens Staphylococcus aureus or Pseudomonas aeruginosa . During exacerbations the relative and absolute abundance of species changed, but not the overall signature. On the average several hundred bacterial and viral species, but just a few fungal species were detected by our pipeline. Five to forty species made up 95% of the bacterial metagenome. Our paradigmatic pilot study demonstrates that whole genome sequencing provides deep insight into the microbial CF lung metagenome. Supported by Mukoviszidose e.V. and the German Center for Lung Research (DZL).