abstract
- Microbial interactions mediating colonization resistance play key roles within the human microbiome, shaping susceptibility to infection from birth. To gain insight into microbiome-mediated defenses and respiratory pathogen colonization dynamics, we sequenced and analyzed nasal (n=229) and oral (n=210) microbiomes with associated health/environmental data from our Wisconsin Infant Study Cohort at age 24-months. Participants with early-life lower respiratory tract infection (LRTI) were more likely to be formula-fed, attend daycare, and experience wheezing. Shotgun metagenomic sequencing with detection of viral and bacterial respiratory pathogens revealed nasal microbiome composition to associate with prior LRTI - namely lower alpha diversity, depletion of Prevotella, and enrichment of Moraxella catarrhalis including drug-resistant strains. Prevotella originating from healthy microbiomes had higher biosynthetic gene cluster abundance and exhibited contact-independent inhibition of M. catarrhalis, suggesting interbacterial competition impacts nasal pathogen colonization. This work advances understanding of protective host-microbial interactions occurring in airway microbiomes that alter infection susceptibility in early-life.