title: Features of the bronchial bacterial microbiome associated with atopy, asthma, and responsiveness to inhaled corticosteroid treatment.
abstract: BACKGROUND
  Compositional differences in the bronchial bacterial microbiota have been associated with asthma, but it remains unclear whether the findings are attributable to asthma, to aeroallergen sensitization, or to inhaled corticosteroid treatment.
  
  
  OBJECTIVE
  We sought to compare the bronchial bacterial microbiota in adults with steroid-naive atopic asthma, subjects with atopy but no asthma, and nonatopic healthy control subjects and to determine relationships of the bronchial microbiota to phenotypic features of asthma.
  
  
  METHODS
  Bacterial communities in protected bronchial brushings from 42 atopic asthmatic subjects, 21 subjects with atopy but no asthma, and 21 healthy control subjects were profiled by using 16S rRNA gene sequencing. Bacterial composition and community-level functions inferred from sequence profiles were analyzed for between-group differences. Associations with clinical and inflammatory variables were examined, including markers of type 2-related inflammation and change in airway hyperresponsiveness after 6 weeks of fluticasone treatment.
  
  
  RESULTS
  The bronchial microbiome differed significantly among the 3 groups. Asthmatic subjects were uniquely enriched in members of the Haemophilus, Neisseria, Fusobacterium, and Porphyromonas species and the Sphingomonodaceae family and depleted in members of the Mogibacteriaceae family and Lactobacillales order. Asthma-associated differences in predicted bacterial functions included involvement of amino acid and short-chain fatty acid metabolism pathways. Subjects with type 2-high asthma harbored significantly lower bronchial bacterial burden. Distinct changes in specific microbiota members were seen after fluticasone treatment. Steroid responsiveness was linked to differences in baseline compositional and functional features of the bacterial microbiome.
  
  
  CONCLUSIONS
  Even in subjects with mild steroid-naive asthma, differences in the bronchial microbiome are associated with immunologic and clinical features of the disease. The specific differences identified suggest possible microbiome targets for future approaches to asthma treatment or prevention.
authors.affiliation: Department of Medicine, Division of Gastroenterology, University of California, San Francisco, Calif.
authors.forename: Juliana
authors.initials: J
authors.lastname: Durack
authors.affiliation: Department of Medicine, Division of Gastroenterology, University of California, San Francisco, Calif.
authors.forename: Susan V
authors.initials: SV
authors.lastname: Lynch
authors.affiliation: Division of Pulmonary & Critical Care Medicine, University of Michigan, Ann Arbor, Mich.
authors.forename: Snehal
authors.initials: S
authors.lastname: Nariya
authors.affiliation: Department of Medicine, University of California, San Francisco, Calif.
authors.forename: Nirav R
authors.initials: NR
authors.lastname: Bhakta
authors.affiliation: Division of Pediatrics, Washington University School of Medicine, St Louis, Mo.
authors.forename: Avraham
authors.initials: A
authors.lastname: Beigelman
authors.affiliation: Division of Pediatrics, Washington University School of Medicine, St Louis, Mo; Division of Pulmonary and Critical Care Medicine, Washington University School of Medicine, St Louis, Mo.
authors.forename: Mario
authors.initials: M
authors.lastname: Castro
authors.affiliation: Department of Public Health Sciences, Penn State University, Hershey, Pa.
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Dyer
authors.affiliation: Department of Medicine, Brigham & Women's Hospital, Boston, Mass.
authors.forename: Elliot
authors.initials: E
authors.lastname: Israel
authors.affiliation: Health Sciences, University of Arizona, Tucson, Ariz.
authors.forename: Monica
authors.initials: M
authors.lastname: Kraft
authors.affiliation: Department of Medicine, National Jewish Hospital, Denver, Colo.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Martin
authors.affiliation: Department of Public Health Sciences, Penn State University, Hershey, Pa.
authors.forename: David T
authors.initials: DT
authors.lastname: Mauger
authors.affiliation: Department of Medicine, Northwestern University, Chicago, Ill.
authors.forename: Sharon R
authors.initials: SR
authors.lastname: Rosenberg
authors.affiliation: Department of Public Health Sciences, Penn State University, Hershey, Pa.
authors.forename: Tonya
authors.initials: T
authors.lastname: Sharp-King
authors.affiliation: Department of Medicine, University of Chicago, Chicago, Ill.
authors.forename: Steven R
authors.initials: SR
authors.lastname: White
authors.affiliation: Department of Medicine, University of California, San Francisco, Calif.
authors.forename: Prescott G
authors.initials: PG
authors.lastname: Woodruff
authors.affiliation: Department of Medicine, Northwestern University, Chicago, Ill.
authors.forename: Pedro C
authors.initials: PC
authors.lastname: Avila
authors.affiliation: Department of Medicine, University of Wisconsin-Madison, Madison, Wis.
authors.forename: Loren C
authors.initials: LC
authors.lastname: Denlinger
authors.affiliation: University of Pittsburgh Asthma Institute at UPMC/UPSOM, Pittsburgh, Pa.
authors.forename: Fernando
authors.initials: F
authors.lastname: Holguin
authors.affiliation: Department of Medicine, University of California, San Francisco, Calif.
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Lazarus
authors.affiliation: Duke Asthma, Allergy & Airway Center, Duke University School of Medicine, Durham, NC.
authors.forename: Njira
authors.initials: N
authors.lastname: Lugogo
authors.affiliation: Wake Forest School of Medicine, Winston-Salem, NC.
authors.forename: Wendy C
authors.initials: WC
authors.lastname: Moore
authors.affiliation: Wake Forest School of Medicine, Winston-Salem, NC.
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Peters
authors.affiliation: Duke Asthma, Allergy & Airway Center, Duke University School of Medicine, Durham, NC.
authors.forename: Loretta
authors.initials: L
authors.lastname: Que
authors.affiliation: Department of Medicine, Northwestern University, Chicago, Ill.
authors.forename: Lewis J
authors.initials: LJ
authors.lastname: Smith
authors.affiliation: Department of Medicine, University of Wisconsin-Madison, Madison, Wis.
authors.forename: Christine A
authors.initials: CA
authors.lastname: Sorkness
authors.affiliation: Department of Medicine, National Jewish Hospital, Denver, Colo.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Wechsler
authors.affiliation: University of Pittsburgh Asthma Institute at UPMC/UPSOM, Pittsburgh, Pa.
authors.forename: Sally E
authors.initials: SE
authors.lastname: Wenzel
authors.affiliation: Department of Medicine, University of California, San Francisco, Calif. Electronic address: homer.boushey@ucsf.edu.
authors.forename: Homer A
authors.initials: HA
authors.lastname: Boushey
authors.affiliation: Division of Pulmonary & Critical Care Medicine, University of Michigan, Ann Arbor, Mich.
authors.forename: Yvonne J
authors.initials: YJ
authors.lastname: Huang
mesh_terms: D000280:Administration, Inhalation; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000328:Adult; D001249:Asthma / Q000188:drug therapy / Q000382:microbiology*; D001419:Bacteria / Q000145:classification / Q000235:genetics / Q000302:isolation & purification; D001980:Bronchi / Q000187:drug effects / Q000382:microbiology*; D005260:Female; D000068298:Fluticasone / Q000627:therapeutic use; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000188:drug therapy / Q000382:microbiology*; D008297:Male; D064307:Microbiota; D008875:Middle Aged; D012329:RNA, Bacterial / Q000235:genetics; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D055815:Young Adult
chemical_list: D000305:Adrenal Cortex Hormones; D012329:RNA, Bacterial; D012336:RNA, Ribosomal, 16S; D000068298:Fluticasone
keywords: 16S ribosomal RNA; Asthma; T(H)2 inflammation; atopy; bacteria; corticosteroids; metabolic pathways; microbiome; short-chain fatty acids; three-gene mean