The administration of intranasal live attenuated influenza vaccine induces changes in the nasal microbiota and nasal epithelium gene expression profiles.

Barbara A. Methé,K. Li,C. Nguyen,K. Saira,Monika Bihan,E. Ghedin,D. Elashoff,S. Hu,X. Wang,Y. Tarabichi,Jane C. Deng,Bryan Frank

doi:10.1186/s40168-015-0133-2

Abstract

BackgroundViral 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 microbiota, we analyzed nasal bacterial composition by 16S ribosomal RNA (rRNA) gene sequencing in healthy adults at baseline and at 1 to 2 weeks and 4 to 6 weeks following instillation of live attenuated influenza vaccine or intranasal sterile saline. A subset of these samples was submitted for microarray host gene expression profiling.ResultsWe 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 genera (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.ConclusionsCollectively, our findings demonstrate that although the human nasal bacterial community is heterogeneous and typically individually robust, activation of a type I interferon (IFN)-mediated antiviral response may foster the disproportionate emergence of potentially pathogenic species such as S. aureus.Trial registrationThis study was registered with Clinicaltrials.gov on 11/3/15, NCT02597647.Electronic supplementary materialThe online version of this article (doi:10.1186/s40168-015-0133-2) contains supplementary material, which is available to authorized users.

Highlights

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
Secondary bacterial pneumonia has been implicated as the main cause of death during influenza pandemics, including the 1918 “Spanish” and 2009 novel H1N1 influenza A virus pandemics [1,2,3]
Murine models have demonstrated that both type I and type II IFN-mediated host responses to influenza infection act to critically suppress the antibacterial response against pulmonary infection by both S. pneumoniae and S. aureus [21,22,23,24,25,26,27]

Summary

Introduction

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. Whether alterations in nasal colonization patterns occur during viral infections in human beings was unknown Such a virally mediated change may permit the emergence or overgrowth of potentially pathogenic bacteria as a precursor to secondary bacterial infection. Further understanding of such a process would be essential towards the development of new interventions or preventative modalities that might depend on tempering the adverse changes in the nasal microbiota and/or host response

Methods

Results

Conclusion