Upper versus lower airway microbiome and metagenome in children with cystic fibrosis and their correlation with lung inflammation

PLoS One. 2019 Sep 19;14(9):e0222323. doi: 10.1371/journal.pone.0222323. eCollection 2019.

Abstract

Objective: Airways of children with cystic fibrosis (CF) harbor complex polymicrobial communities which correlates with pulmonary disease progression and use of antibiotics. Throat swabs are widely used in young CF children as a surrogate to detect potentially pathogenic microorganisms in lower airways. However, the relationship between upper and lower airway microbial communities remains poorly understood. This study aims to determine (1) to what extent oropharyngeal microbiome resembles the lung microbiome in CF children and (2) if lung microbiome composition correlates with airway inflammation.

Method: Throat swabs and bronchoalveolar lavage (BAL) were obtained concurrently from 21 CF children and 26 disease controls. Oropharyngeal and lung microbiota were analyzed using 16S rRNA deep sequencing and correlated with neutrophil counts in BAL and antibiotic exposure.

Results: Oropharyngeal microbial communities clustered separately from lung communities and had higher microbial diversity (p < 0.001). CF microbiome differed significantly from non-CF controls, with a higher abundance of Proteobacteria in both upper and lower CF airways. Neutrophil count in the BAL correlated negatively with the diversity but not richness of the lung microbiome. In CF children, microbial genes involved in bacterial motility proteins, two-component system, flagella assembly, and secretion system were enriched in both oropharyngeal and lung microbiome, whereas genes associated with synthesis and metabolism of nucleic acids and protein dominated the non-CF controls.

Conclusions: This study identified a unique microbial profile with altered microbial diversity and metabolic functions in CF airways which is significantly affected by airway inflammation. These results highlight the limitations of using throat swabs as a surrogate to study lower airway microbiome and metagenome in CF children.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bronchoalveolar Lavage Fluid / microbiology
  • Bronchoscopy
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Cystic Fibrosis / microbiology*
  • Cystic Fibrosis / pathology
  • Female
  • Humans
  • Lung / microbiology*
  • Lung / pathology
  • Male
  • Microbiota* / genetics
  • Oropharynx / microbiology*
  • Pharynx / microbiology
  • Pneumonia / microbiology*
  • RNA, Ribosomal, 16S / genetics

Substances

  • RNA, Ribosomal, 16S

Grants and funding

This work was supported by the Gatorade Trust through funds distributed by the University of Florida, Department of Medicine to GPW. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.