LAUSR

Introduction: The traditional paradigm that the lung is a sterile environment no longer holds true in the current era of the microbiome. Aim: Our aim was to describe the lower airway microbiome in pre-school children with CF. Methods: Prospectively recruited children with CF had a broncho-alveolar lavage (BAL) sample and cough swab obtained as part of their annual review. A comparative BAL sample was obtained from non-CF control subjects. Clinical data, BAL culture and inflammatory markers were compared with microbiome data obtained using 16S rRNA amplification on MiSeq Illumina sequencer. OTUs were aligned using PyNAS. Alpha-diversity and beta-diversity were calculated using Qiime. Taxonomy was assigned using a BLAST search against the SILVA SSU 123 database. Further bioinformatics was performed with the phyloseq package in R.3.2.2. Results: Data on 291 sequenced BALs from 50 controls (mean age 6.1 years) and 106 CFs (mean age 3.6 years) shows the CF lower airway microbiome is distinct from the non-CF, has lower diversity, and different relative abundance at phylum, family and genus level. Staphylococcus and Pseudomonas genus were more abundant in CF. There was a significant negative correlation between alpha diversity and IL-8 (R=-0.21 p=-0.01) and neutrophil elastase (R=-0.17, p=0.03). BAL and cough swabs represent different microbiomes on Bray Curtis PCoA plot (R2 = 0.11, p=0.01). Even in a young CF cohort increasing age was associated with reducing diversity. Neither flucloxacillin nor azithromycin taken on the day of bronchoscopy, or previous oral or IV antibiotics, significantly altered the microbiome. Conclusion: The CF lower airway microbiome is altered early in life