Background: Progressive respiratory diseases are characterised by chronic infections. Shotgun metagenomics identifies bacteria, fungi and DNA viruses at higher resolution than amplicon sequencing commonly applied to study this habitat.

Question: The airway metagenome of preterm infants (n=24), healthy adults (n=88) and people with bronchiectasis (n=101) was examined to identify microbial community members that distinguish disease from lung health.

Methods: Shotgun metagenomics sequencing was performed on an Illumina NextSeq system. The generated short read data sets were then processed by our in-house developed sequencing alignment pipeline Wochenende.

Results: During their stay at the neonatal intensive care unit, preterm neonates acquired individual non-maternal airway metagenome signatures from the hospital environment. After hospital discharge, airway metagenomes developed towards a common taxonomic structure, but did not achieve the stable bacterial community structures seen in healthy full-term infants. In case of the people with bronchiectasis, the individual metagenomes clustered by the absence or presence of H. influenzae and P. aeruginosa. Severe bronchiectasis was characterised by low diversity metagenomes. Comparison with the sputum metagenome of healthy non-smokers revealed a gradient of depletion of commensal taxa in bronchiectasis, even in the absence of any respiratory pathogen.

Conclusions: As signs of microbial dysbiosis, commensal species become gradually suppressed in people with bronchiectasis and the bacterial metagenome of preterm infants is still immature by 15 months of age.