Abstract

The metagenome development of the human respiratory tract was investigated by shotgun metagenome metagenomic sequencing of cough swabs from healthy children and children with cystic fibrosis (CF) between 3 weeks and 6 years of age. A healthy microbial community signature was associated with increased absolute abundances in terms of bacterial–human cell ratios of core and rare species across all age groups, with a higher diversity of rare species and a tightly interconnected species co-occurrence network, in which individual members were found in close proximity to each other and negative correlations were absent. Even without typical CF pathogens, the CF infant co-occurrence network was found to be less stable and prone to fragmentation due to fewer connections between species, a higher number of bridging species and the presence of negative species correlations. Detection of low-abundant DNA of the CF hallmark pathogen Pseudomonas aeruginosa was neither disease- nor age-associated in our cohort. Healthy and CF children come into contact with P. aeruginosa on a regular basis and from early on.

Highlights

  • Until recently the human lower airways have been considered to be sterile and most studies investigated the lung microbiology in conditions of acute infections or chronic lung disease, such as cystic fibrosis (CF)[1,2,3,4,5,6,7,8,9,10]

  • A range of CF respiratory tract microbiome studies has been published to investigate the microbial communities inhabiting the diseased respiratory tract in children[2,3,4,5,6,7,8,9,10]. These studies have applied partial 16 S 16S ribosomal RNA gene sequencing for taxonomic classification, which can lead to various taxonomic outcomes depending on the hypervariable region of amplification[39,40,41]

  • We applied deep shotgun metagenomic sequencing based on single-end reads of 75 bp length

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Summary

Introduction

Until recently the human lower airways have been considered to be sterile and most studies investigated the lung microbiology in conditions of acute infections or chronic lung disease, such as cystic fibrosis (CF)[1,2,3,4,5,6,7,8,9,10]. We have observed in a previous metagenome study that P. aeruginosa-DNA was present in the respiratory secretions of all pancreatic insufficient (PI) CF patients aged 6 years or older in at least minute amounts, while P. aeruginosa was not detectable by culture-dependent diagnostics[19]. Again, it remains unknown when the CF children come into contact with the CF hallmark pathogen for the first time

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