title: Eosinophilic airway inflammation in asthmatic patients is associated with an altered airway microbiome.
abstract: BACKGROUND
  Asthmatic patients have higher microbiome diversity and an altered composition, with more Proteobacteria and less Bacteroidetes compared with healthy control subjects. Studies comparing airway inflammation and the airway microbiome are sparse, especially in subjects not receiving anti-inflammatory treatment.
  
  
  OBJECTIVE
  We sought to describe the relationship between the airway microbiome and patterns of airway inflammation in steroid-free patients with asthma and healthy control subjects.
  
  
  METHODS
  Bronchoalveolar lavage fluid was collected from 23 steroid-free nonsmoking patients with asthma and 10 healthy control subjects. Bacterial DNA was extracted from and subjected to Illumina MiSeq sequencing of the 16S rDNA V4 region. Eosinophils and neutrophils in the submucosa were quantified by means of immunohistochemical identification and computerized image analysis. Induced sputum was obtained, and airway hyperresponsiveness to mannitol and fraction of exhaled nitric oxide values were measured. Relationships between airway microbial diversity and composition and inflammatory profiles were analyzed.
  
  
  RESULTS
  In asthmatic patients airway microbial composition was associated with airway eosinophilia and AHR to mannitol but not airway neutrophilia. The overall composition of the airway microbiome of asthmatic patients with the lowest levels of eosinophils but not asthmatic patients with the highest levels of eosinophils deviated significantly from that of healthy subjects. Asthmatic patients with the lowest levels of eosinophils had an altered bacterial abundance profile, with more Neisseria, Bacteroides, and Rothia species and less Sphingomonas, Halomonas, and Aeribacillus species compared with asthmatic patients with more eosinophils and healthy control subjects.
  
  
  CONCLUSIONS
  The level of eosinophilic airway inflammation correlates with variations in the microbiome across asthmatic patients, whereas neutrophilic airway inflammation does not. This warrants further investigation on molecular pathways involved in both patients with eosinophilic and those with noneosinophilic asthma.
authors.affiliation: University Hospital Bispebjerg, Copenhagen, Denmark. Electronic address: asgersverrild@gmail.com.
authors.forename: Asger
authors.initials: A
authors.lastname: Sverrild
authors.affiliation: Department of Biology, University of Copenhagen, Denmark.
authors.forename: Pia
authors.initials: P
authors.lastname: Kiilerich
authors.affiliation: Department of Biology, University of Copenhagen, Denmark.
authors.forename: Asker
authors.initials: A
authors.lastname: Brejnrod
authors.affiliation: Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Pedersen
authors.affiliation: University Hospital Bispebjerg, Copenhagen, Denmark.
authors.forename: Celeste
authors.initials: C
authors.lastname: Porsbjerg
authors.affiliation: Respiratory Medicine and Allergology and Experimental Medical Science, Lund University, Lund, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Bergqvist
authors.affiliation: Respiratory Medicine and Allergology and Experimental Medical Science, Lund University, Lund, Sweden.
authors.forename: Jonas S
authors.initials: JS
authors.lastname: Erjefält
authors.affiliation: Department of Biology, University of Copenhagen, Denmark.
authors.forename: Karsten
authors.initials: K
authors.lastname: Kristiansen
authors.affiliation: University Hospital Bispebjerg, Copenhagen, Denmark.
authors.forename: Vibeke
authors.initials: V
authors.lastname: Backer
mesh_terms: D000328:Adult; D001249:Asthma / Q000276:immunology / Q000378:metabolism / Q000382:microbiology* / Q000503:physiopathology; D001419:Bacteria / Q000235:genetics / Q000302:isolation & purification; D001992:Bronchoalveolar Lavage Fluid / Q000382:microbiology; D004269:DNA, Bacterial / Q000032:analysis; D004802:Eosinophilia / Q000276:immunology / Q000378:metabolism / Q000382:microbiology* / Q000503:physiopathology; D004804:Eosinophils / Q000276:immunology; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D007958:Leukocyte Count; D008297:Male; D008353:Mannitol / Q000494:pharmacology; D064307:Microbiota; D009504:Neutrophils / Q000276:immunology; D009569:Nitric Oxide / Q000378:metabolism; D013183:Sputum / Q000166:cytology; D055815:Young Adult
chemical_list: D004269:DNA, Bacterial; D009569:Nitric Oxide; D008353:Mannitol
keywords: Airway inflammation; asthma; bacteria; bronchoalveolar lavage; microbiome; noneosinophilic asthma