Nasal microbiome and phageome profiles are associated with prospective respiratory viral infection risk in school-age children.

Abstract

Respiratory viral infections are common and can trigger asthma exacerbations in children. The roles of the nasal microbiome and phageome (viruses that infect microbes) are not well understood. We sought to characterize the epidemiology of respiratory viral infections and the interplay between the nasal microbiome, phageome, and viral infections in school-age children with asthma. We performed metagenomic sequencing and quantitative RT-PCR detection of respiratory viruses on 375 nasal samples from 227 school-age children with asthma collected routinely 3 times over a year. Surveys on parent-reported cold and asthma symptoms were administered routinely every 2 months. We evaluated multikingdom changes to the nasal microbiome during infection. A sparse partial least-squares discriminant analysis model identified microbial signatures associated with prospective viral infection risk. Respiratory viruses were identified in 124 (33%) samples, with rhinovirus being the most prevalent. Cold and asthma symptoms within the previous 14 days had a sensitivity of 79% and 59%, respectively, for quantitative RT-PCR-confirmed infection. Respiratory viral infection increased asthma symptoms and was accompanied by loss of nasal bacterial diversity and a reproducible bloom of pathobionts with no change in the mycobiome or phageome. A baseline bacteriome-dominated profile was protective (adjusted odds ratio, 0.41 [95% CI, 0.25-0.67]; P < .001), whereas phageome profiles increased risk (adjusted odds ratio, 3.74 [95% CI, 1.85-7.55]; P < .001) of viral infection. Specific phages inversely correlated with Staphylococcus epidermidis abundance, the most protective commensal against infection risk. The nasal microbiome and phageome exert opposing influences on respiratory viral infection risk, highlighting their potential roles in modulating susceptibility to viral infections.