鼻微生物组和噬菌体组特征与学龄儿童未来呼吸道病毒感染风险相关

Background: 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. Objective: To characterize the epidemiology of respiratory viral infections and the interplay between the nasal microbiome, phageome, and viral infections in school-aged children with asthma. Methods: We performed metagenomic sequencing and RT-qPCR detection of respiratory viruses on 375 nasal samples from 227 school-age children with asthma collected routinely three times over one year. Surveys on parent-reported cold and asthma symptoms were administered routinely every two months. We evaluated multi-kingdom changes to the nasal microbiome during infection. A sPLS-DA model identified microbial signatures associated with prospective viral infection risk. Results: Respiratory viruses were identified in 124 (33%) samples, with rhinovirus most prevalent. Cold and asthma symptoms within the prior 14 days had a sensitivity of 79% and 59%, respectively, for RT-qPCR-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 OR 0.41 [95% CI, 0.25 - 0.67]; P < 0.001), whereas phageome profiles increased risk (adjusted OR 3.74 [1.85 - 7.55]; P < 0.001) of viral infection. Specific phages inversely correlated with Staphylococcus epidermidis abundance, the most protective commensal against infection risk. Conclusion: The nasal microbiome and phageome exert opposing influences on respiratory viral infection risk, highlighting their potential roles in modulating susceptibility to viral infections.