title: Host Response to the Lung Microbiome in Chronic Obstructive Pulmonary Disease.
abstract: BACKGROUND
  The relatively sparse but diverse microbiome in human lungs may become less diverse in chronic obstructive pulmonary disease (COPD). This article examines the relationship of this microbiome to emphysematous tissue destruction, number of terminal bronchioles, infiltrating inflammatory cells, and host gene expression.
  
  
  METHODS
  Culture-independent pyrosequencing microbiome analysis was used to examine the V3-V5 regions of bacterial 16S ribosomal DNA in 40 samples of lung from 5 patients with COPD (Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage 4) and 28 samples from 4 donors (controls). A second protocol based on the V1-V3 regions was used to verify the bacterial microbiome results. Within lung tissue samples the microbiome was compared with results of micro-computed tomography, infiltrating inflammatory cells measured by quantitative histology, and host gene expression.
  
  
  RESULTS
  Ten operational taxonomic units (OTUs) was found sufficient to discriminate between control and GOLD stage 4 lung tissue, which included known pathogens such as Haemophilus influenzae. We also observed a decline in microbial diversity that was associated with emphysematous destruction, remodeling of the bronchiolar and alveolar tissue, and the infiltration of the tissue by CD4(+) T cells. Specific OTUs were also associated with neutrophils, eosinophils, and B-cell infiltration (P < 0.05). The expression profiles of 859 genes and 235 genes were associated with either enrichment or reductions of Firmicutes and Proteobacteria, respectively, at a false discovery rate cutoff of less than 0.1.
  
  
  CONCLUSIONS
  These results support the hypothesis that there is a host immune response to microorganisms within the lung microbiome that appears to contribute to the pathogenesis of COPD.
authors.affiliation: 1 Centre for Heart Lung Innovation, Providence Heart + Lung Institute at St. Paul's Hospital, Vancouver, British Columbia, Canada.|2 Department of Medicine.
authors.forename: Marc A
authors.initials: MA
authors.lastname: Sze
authors.affiliation: 3 Department of Microbiology and Immunology, Life Sciences Institute, and.
authors.forename: Pedro A
authors.initials: PA
authors.lastname: Dimitriu
authors.affiliation: 1 Centre for Heart Lung Innovation, Providence Heart + Lung Institute at St. Paul's Hospital, Vancouver, British Columbia, Canada.|4 Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Masaru
authors.initials: M
authors.lastname: Suzuki
authors.affiliation: 1 Centre for Heart Lung Innovation, Providence Heart + Lung Institute at St. Paul's Hospital, Vancouver, British Columbia, Canada.|2 Department of Medicine.
authors.forename: John E
authors.initials: JE
authors.lastname: McDonough
authors.affiliation: 5 Division of Computational Biomedicine, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts.
authors.forename: Josh D
authors.initials: JD
authors.lastname: Campbell
authors.affiliation: 5 Division of Computational Biomedicine, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts.
authors.forename: John F
authors.initials: JF
authors.lastname: Brothers
authors.affiliation: 6 Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan; and.
authors.forename: John R
authors.initials: JR
authors.lastname: Erb-Downward
authors.affiliation: 6 Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan; and.
authors.forename: Gary B
authors.initials: GB
authors.lastname: Huffnagle
authors.affiliation: 1 Centre for Heart Lung Innovation, Providence Heart + Lung Institute at St. Paul's Hospital, Vancouver, British Columbia, Canada.|4 Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Shizu
authors.initials: S
authors.lastname: Hayashi
authors.affiliation: 1 Centre for Heart Lung Innovation, Providence Heart + Lung Institute at St. Paul's Hospital, Vancouver, British Columbia, Canada.|2 Department of Medicine.
authors.forename: W Mark
authors.initials: WM
authors.lastname: Elliott
authors.affiliation: 7 Department of Cardiovascular and Thoracic Surgery, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Joel
authors.initials: J
authors.lastname: Cooper
authors.affiliation: 1 Centre for Heart Lung Innovation, Providence Heart + Lung Institute at St. Paul's Hospital, Vancouver, British Columbia, Canada.|2 Department of Medicine.
authors.forename: Don D
authors.initials: DD
authors.lastname: Sin
authors.affiliation: 5 Division of Computational Biomedicine, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts.
authors.forename: Marc E
authors.initials: ME
authors.lastname: Lenburg
authors.affiliation: 5 Division of Computational Biomedicine, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts.
authors.forename: Avrum
authors.initials: A
authors.lastname: Spira
authors.affiliation: 3 Department of Microbiology and Immunology, Life Sciences Institute, and.
authors.forename: William W
authors.initials: WW
authors.lastname: Mohn
authors.affiliation: 1 Centre for Heart Lung Innovation, Providence Heart + Lung Institute at St. Paul's Hospital, Vancouver, British Columbia, Canada.|4 Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: James C
authors.initials: JC
authors.lastname: Hogg
mesh_terms: D055745:Bronchioles / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008297:Male; D064307:Microbiota; D008875:Middle Aged; D020556:Neutrophil Infiltration; D029424:Pulmonary Disease, Chronic Obstructive / Q000276:immunology / Q000382:microbiology* / Q000473:pathology*
keywords: COPD; bacteria; inflammation; microbiome