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The Lung Microbiome in Young Children with Cystic Fibrosis: A Prospective Cohort Study
Linnane, Barry Walsh, Aaron M. Walsh, Calum J. Crispie, Fiona O’Sullivan, Orla Cotter, Paul D. McDermott, Michael Renwick, Julie McNally, Paul
Linnane, Barry
Walsh, Aaron M.
Walsh, Calum J.
Crispie, Fiona
O’Sullivan, Orla
Cotter, Paul D.
McDermott, Michael
Renwick, Julie
McNally, Paul
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2021-02-26
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Linnane B, Walsh AM, Walsh CJ, et al. The Lung Microbiome in Young Children with Cystic Fibrosis: A Prospective Cohort Study. Microorganisms 2021;9(3):492. doi: https://doi.org/10.3390/microorganisms9030492
Abstract
The cystic fibrosis (CF) lung harbours a diverse microbiome and reduced diversity in the CF
lung has been associated with advancing age, increased inflammation and poorer lung function. Data
suggest that the window for intervention is early in CF, yet there is a paucity of studies on the lung
microbiome in children with CF. The objective of this study was to thoroughly characterise the lower
airway microbiome in pre-school children with CF. Bronchoalveolar lavage (BAL) samples were
collected annually from children attending the three clinical centres. Clinical and demographic data
were collated on all subjects alongside BAL inflammatory markers. 16S rRNA gene sequencing was
performed on the Illumina MiSeq platform. Bioinformatics and data analysis were performed using
Qiime and R project software. Data on 292 sequenced BALs from 101 children with CF and 51 without
CF show the CF lung microbiome, while broadly similar to that in non-CF children, is distinct.
Alpha diversity between the two cohorts was indistinguishable at this early age. The CF diagnosis
explained only 1.1% of the variation between the cohort microbiomes. However, several key genera
were significantly differentially abundant between the groups. While the non-CF lung microbiome
diversity increased with age, diversity reduced in CF with age. Pseudomonas and Staphylococcus were
more abundant with age, while genera such as Streptococcus, Porphyromonas and Veillonella were less
abundant with age. There was a negative correlation between alpha diversity and interleukin-8 and
neutrophil elastase in the CF population. Neither current flucloxacillin or azithromycin prophylaxis,
nor previous oral or IV antibiotic exposure, was correlated with microbiome diversity. Consecutive
annual BAL samples over 5 years from a subgroup of children demonstrated diverse patterns of
development in the first years of life.