The human respiratory tract microbial community structures in healthy and cystic fibrosis infants

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.

Bacterial low-abundant taxa are key determinants of a healthy airway metagenome in the early years of human life

“…We re-analysed our previously published shotgun metagenomic sequencing data obtained from deep cough swabs of 41 CF and 46 healthy children between zero and six years of age (ENA PRJEB38221) [26] . As previously reported, the clinical study was approved by the ethics committee of MHH (No.…”

“…Sampling was accompanied by an obligate cough of the participant. The samples were immediately stored at −80 °C until further processed with negative controls and sequenced on the Illumina NextSeq 500/550 platform to generate short (75 bp) single-end reads [26] .…”

“…Undirected ecological network analysis was based on the best practice guidelines for species co-occurrence network construction [26] , [48] . Spearman’s rank correlation matrices were obtained for healthy and CF children from BCPHC-, RLE- or VST-normalised count data of background core and rare species as defined by the 25th abundance percentile and confirmed by both reference databases.…”

“…We therefore assumed that rare species of healthy and diseased human airways in the early years of life occupy a similar pivotal role in their microbial community. With the objective to investigate the development of the rare species biosphere and unravel the yet unknown contribution of rare species to healthy or chronically diseased airway habitats, we re-analysed publicly available cross-sectional metagenome data obtained from deep cough swabs of 46 healthy children, 41 children with cystic fibrosis (CF) and negative controls [26] . Our recent software publication raspir in combination with gapseq , a tool introduced by Zimmermann et al (2021) facilitated the taxonomic and functional identification of core and rare species from shotgun metagenomic sequencing data and reference genomes, respectively, with reduced false discovery and omission rates [27] , [28] .…”

Metaproteomics to Decipher CF Host-Microbiota Interactions: Overview, Challenges and Future Perspectives

“…Within the CF lung habitat, metagenomics studies reveal a broad repertoire of viruses, moulds, fungi, archaea, and bacteria [38][39][40]. These data allowed the classification of a larger proportion of microbiome inhabitants at the species level and prominent CF pathogens at the strain level, as well as the detection of multiple subpopulations of specific pathogens [39,[41][42][43] (Figure 1). Recently, Bacci et al [42] and Dmitrijeva et al [40] used shotgun metagenomics approaches to track the temporal dynamics of the sputum microbiome.…”