Early-life upper airway microbiota are associated with decreased lower respiratory tract infections

BACKGROUND: Microbial interactions mediating colonization resistance play key roles within the human microbiome, shaping susceptibility to infection from birth. The role of the nasal and oral microbiome in the context of early life respiratory infections and subsequent allergic disease risk remains understudied. OBJECTIVES: Our aim was to gain insight into microbiome-mediated defenses and respiratory pathogen colonization dynamics within the upper respiratory tract during infancy. METHODS: We performed shotgun metagenomic sequencing of nasal (n = 229) and oral (n = 210) microbiomes from our Wisconsin Infant Study Cohort at age 24 months and examined the influence of participant demographics and exposure history on microbiome composition. Detection of viral and bacterial respiratory pathogens by RT-PCR and culture-based studies with antibiotic susceptibility testing, respectively, to assess pathogen carriage was performed. Functional bioassays were used to evaluate pathogen inhibition by respiratory tract commensals. RESULTS: Participants with early-life lower respiratory tract infection were more likely to be formula fed, attend day care, and experience wheezing. Composition of the nasal, but not oral, microbiome associated with prior lower respiratory tract infection, 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. CONCLUSIONS: These results suggest interbacterial competition affects nasal pathogen colonization. This work advances understanding of protective host-microbe interactions occurring in airway microbiomes that alter infection susceptibility in early life.