title: The adult nasopharyngeal microbiome as a determinant of pneumococcal acquisition.
abstract: BACKGROUND
  Several cohort studies have indicated associations between S. pneumoniae and other microbes in the nasopharynx. To study causal relationships between the nasopharyngeal microbiome and pneumococcal carriage, we employed an experimental human pneumococcal carriage model. Healthy adult volunteers were assessed for pneumococcal carriage by culture of nasal wash samples (NWS). Those without natural pneumococcal carriage received an intranasal pneumococcal inoculation with serotype 6B or 23F. The composition of the nasopharyngeal microbiome was longitudinally studied by 16S rDNA pyrosequencing on NWS collected before and after challenge.
  
  
  RESULTS
  Among 40 selected volunteers, 10 were natural carriers and 30 were experimentally challenged. At baseline, five distinct nasopharyngeal microbiome profiles were identified. The phylogenetic distance between microbiomes of natural pneumococcal carriers was particularly large compared to non-carriers. A more diverse microbiome prior to inoculation was associated with the establishment of pneumococcal carriage. Perturbation of microbiome diversity upon pneumococcal challenge was strain specific. Shifts in microbiome profile occurred after pneumococcal exposure, and those volunteers who acquired carriage more often diverted from their original profile. S. pneumoniae was little prominent in the microbiome of pneumococcal carriers.
  
  
  CONCLUSIONS
  Pneumococcal acquisition in healthy adults is more likely to occur in a diverse microbiome and appears to promote microbial heterogeneity.
authors: Laboratory of Pediatric Infectious Diseases, Department of Pediatrics, Radboudumc, 6500 HB Nijmegen, The Netherlands.
authors: Amelieke Jh
authors: AJ
authors: Cremers
authors: Laboratory of Pediatric Infectious Diseases, Department of Pediatrics, Radboudumc, 6500 HB Nijmegen, The Netherlands ; Centre for Molecular and Biomolecular Informatics (CMBI) Bacterial Genomics, Radboudumc, 6500 HB Nijmegen, The Netherlands.
authors: Aldert L
authors: AL
authors: Zomer
authors: Department of Clinical Sciences, Liverpool School of Tropical Medicine, L3 5QA Liverpool, UK.
authors: Jenna F
authors: JF
authors: Gritzfeld
authors: Laboratory of Pediatric Infectious Diseases, Department of Pediatrics, Radboudumc, 6500 HB Nijmegen, The Netherlands.
authors: Gerben
authors: G
authors: Ferwerda
authors: Centre for Molecular and Biomolecular Informatics (CMBI) Bacterial Genomics, Radboudumc, 6500 HB Nijmegen, The Netherlands ; NIZO food research B.V., 6710 BA Ede, The Netherlands.
authors: Sacha Aft
authors: SA
authors: van Hijum
authors: Department of Clinical Sciences, Liverpool School of Tropical Medicine, L3 5QA Liverpool, UK.
authors: Daniela M
authors: DM
authors: Ferreira
authors: Hubert Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, GA 30322 USA.
authors: Joshua R
authors: JR
authors: Shak
authors: Hubert Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, GA 30322 USA.
authors: Keith P
authors: KP
authors: Klugman
authors: Centre for Molecular and Biomolecular Informatics (CMBI) Bacterial Genomics, Radboudumc, 6500 HB Nijmegen, The Netherlands ; NIZO food research B.V., 6710 BA Ede, The Netherlands.
authors: Jos
authors: J
authors: Boekhorst
authors: NIZO food research B.V., 6710 BA Ede, The Netherlands.
authors: Harro M
authors: HM
authors: Timmerman
authors: Laboratory of Pediatric Infectious Diseases, Department of Pediatrics, Radboudumc, 6500 HB Nijmegen, The Netherlands.
authors: Marien I
authors: MI
authors: de Jonge
authors: Department of Clinical Sciences, Liverpool School of Tropical Medicine, L3 5QA Liverpool, UK.
authors: Stephen B
authors: SB
authors: Gordon
authors: Laboratory of Pediatric Infectious Diseases, Department of Pediatrics, Radboudumc, 6500 HB Nijmegen, The Netherlands ; Crucell - Johnson & Johnson, Leiden, The Netherlands.
authors: Peter Wm
authors: PW
authors: Hermans
keywords: Experimental human model; Microbiome; Nasopharyngeal carriage; Streptococcus pneumoniae