title: The administration of intranasal live attenuated influenza vaccine induces changes in the nasal microbiota and nasal epithelium gene expression profiles.
abstract: BACKGROUND
  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 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.
  
  
  RESULTS
  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 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.
  
  
  CONCLUSIONS
  Collectively, 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.
  
  
  BACKGROUND
  This study was registered with Clinicaltrials.gov on 11/3/15, NCT02597647 .
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, David Geffen SOM at UCLA, 37-131 CHS, 10833 Le Conte Avenue, Los Angeles, CA, 90095, USA. YTarabichi@mednet.ucla.edu.
authors.forename: Y
authors.initials: Y
authors.lastname: Tarabichi
authors.affiliation: Department of Human Genome Medicine, J. Craig Venter Institute, 9704 Medical Center Drive, Rockville, MD, 20850, USA. KLi@jcvi.org.|Department of Microbial and Environmental Genomics, J. Craig Venter Institute, 9704 Medical Center Drive, Rockville, MD, 20850, USA. KLi@jcvi.org.
authors.forename: K
authors.initials: K
authors.lastname: Li
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, David Geffen SOM at UCLA, 37-131 CHS, 10833 Le Conte Avenue, Los Angeles, CA, 90095, USA. SHu@mednet.ucla.edu.
authors.forename: S
authors.initials: S
authors.lastname: Hu
authors.affiliation: Department of Medicine, UCLA, Los Angeles, CA, USA. chr.d.nguyen@gmail.com.
authors.forename: C
authors.initials: C
authors.lastname: Nguyen
authors.affiliation: Department of Medicine Statistics Core, UCLA, Los Angeles, CA, USA. XYWang@mednet.ucla.edu.
authors.forename: X
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Medicine Statistics Core, UCLA, Los Angeles, CA, USA. DElashoff@mednet.ucla.edu.
authors.forename: D
authors.initials: D
authors.lastname: Elashoff
authors.affiliation: Department of Computational and Systems Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. sairakazima@gmail.com.|Present address: Infectious Disease Research, Southern Research Institute, Birmingham, AL, USA. sairakazima@gmail.com.
authors.forename: K
authors.initials: K
authors.lastname: Saira
authors.affiliation: Department of Human Genome Medicine, J. Craig Venter Institute, 9704 Medical Center Drive, Rockville, MD, 20850, USA. bfrank@jcvi.org.|Department of Microbial and Environmental Genomics, J. Craig Venter Institute, 9704 Medical Center Drive, Rockville, MD, 20850, USA. bfrank@jcvi.org.
authors.forename: Bryan
authors.initials: B
authors.lastname: Frank
authors.affiliation: Department of Human Genome Medicine, J. Craig Venter Institute, 9704 Medical Center Drive, Rockville, MD, 20850, USA. mbihan@jcvi.org.|Department of Microbial and Environmental Genomics, J. Craig Venter Institute, 9704 Medical Center Drive, Rockville, MD, 20850, USA. mbihan@jcvi.org.
authors.forename: Monika
authors.initials: M
authors.lastname: Bihan
authors.affiliation: Department of Computational and Systems Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. eg121@nyu.edu.|Department of Biology, Center for Genomics and Systems Biology, Global Institute of Public Health, New York University, New York, NY, USA. eg121@nyu.edu.
authors.forename: E
authors.initials: E
authors.lastname: Ghedin
authors.affiliation: Department of Human Genome Medicine, J. Craig Venter Institute, 9704 Medical Center Drive, Rockville, MD, 20850, USA. bmethe@jcvi.org.|Department of Microbial and Environmental Genomics, J. Craig Venter Institute, 9704 Medical Center Drive, Rockville, MD, 20850, USA. bmethe@jcvi.org.
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Methé
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, David Geffen SOM at UCLA, 37-131 CHS, 10833 Le Conte Avenue, Los Angeles, CA, 90095, USA. jdeng@mednet.ucla.edu.
authors.forename: Jane C
authors.initials: JC
authors.lastname: Deng
mesh_terms: D000281:Administration, Intranasal; D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D001439:Bacteroides / Q000235:genetics / Q000302:isolation & purification; D005260:Female; D020869:Gene Expression Profiling; D064368:Healthy Volunteers; D006801:Humans; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000276:immunology; D007370:Interferon Type I / Q000235:genetics; D008297:Male; D051379:Mice; D064307:Microbiota / Q000502:physiology*; D008875:Middle Aged; D009297:Nasal Mucosa / Q000276:immunology* / Q000382:microbiology*; D011070:Poly I-C / Q000008:administration & dosage / Q000276:immunology; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D053633:Receptor, Interferon alpha-beta / Q000172:deficiency; D013203:Staphylococcal Infections / Q000382:microbiology; D013210:Staphylococcus / Q000145:classification / Q000235:genetics / Q000302:isolation & purification; D015854:Up-Regulation; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000276:immunology; D055815:Young Adult
chemical_list: D007252:Influenza Vaccines; D007370:Interferon Type I; D012336:RNA, Ribosomal, 16S; D014613:Vaccines, Attenuated; D053633:Receptor, Interferon alpha-beta; D011070:Poly I-C