UCLA

Viral infections such as influenza have been shown to predispose hosts to increased colonization of the respiratory tract by pathogenic bacteria and secondary bacterial pneumonia. To examine how viral infections and host antiviral immune responses alter the upper respiratory microbiome, we analyzed the nasal bacterial composition in healthy volunteers at baseline, 1-2 weeks, and 4-6 weeks after instillation of a live attenuated influenza vaccine or intranasal sterile saline. In parallel, we also assessed changes in the nasal microbiome over similar time points in patients presenting with flu-like illness in ambulatory settings. All samples were subjected to 16S rRNA gene sequencing for assessment of the microbiota, while a subset of samples from vaccinated subjects was submitted for microarray host gene expression profiling. We found that live attenuated influenza vaccination led to significant changes in microbial community structure, diversity and core taxonomic membership as well as increases in the relative abundances of Staphylococcus and Bacteroides (both p<0.05). Hypergeometric testing for the enrichment of gene ontology terms in the vaccinated group reflected a robust up-regulation of type I and type II interferon stimulated genes in the vaccinated group relative to controls. Translational murine studies showed that poly I:C administration did in fact permit greater nasal Staphylococcus aureus persistence, a response absent in interferon alpha/beta receptor deficient mice. Collectively, our findings demonstrate that although the human nasopharyngeal bacterial community is heterogeneous and typically individually robust, activation of an antiviral immune response may foster the disproportionate emergence of potentially pathogenic species such as S. aureus.