title: The lung tissue microbiome in chronic obstructive pulmonary disease.
abstract: BACKGROUND
  Based on surface brushings and bronchoalveolar lavage fluid, Hilty and coworkers demonstrated microbiomes in the human lung characteristic of asthma and chronic obstructive pulmonary disease (COPD), which have now been confirmed by others.
  
  
  OBJECTIVE
  To extend these findings to human lung tissue samples.
  
  
  METHODS
  DNA from lung tissue samples was obtained from nonsmokers (n = 8); smokers without COPD (n = 8); patients with very severe COPD (Global Initiative for COPD [GOLD] 4) (n = 8); and patients with cystic fibrosis (CF) (n = 8). The latter served as a positive control, with sterile water as a negative control. All bacterial community analyses were based on polymerase chain reaction amplifying 16S rRNA gene fragments. Total bacterial populations were measured by quantitative polymerase chain reaction and bacterial community composition was assessed by terminal restriction fragment length polymorphism analysis and pyrotag sequencing.
  
  
  RESULTS
  Total bacterial populations within lung tissue were small (20-1,252 bacterial cells per 1,000 human cells) but greater in all four sample groups versus the negative control group (P < 0.001). Terminal restriction fragment length polymorphism analysis and sequencing distinguished three distinct bacterial community compositions: one common to the nonsmoker and smoker groups, a second to the GOLD 4 group, and the third to the CF-positive control group. Pyrotag sequencing identified greater than 1,400 unique bacterial sequences and showed an increase in the Firmicutes phylum in GOLD 4 patients versus all other groups (P < 0.003) attributable to an increase in the Lactobacillus genus (P < 0.0007).
  
  
  CONCLUSIONS
  There is a detectable bacterial community within human lung tissue that changes in patients with very severe COPD.
authors.affiliation: The James Hogg Research Centre, Providence Heart-Lung Institute at St. Paul’s Hospital, Departments of Medicine and Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Marc A
authors.initials: MA
authors.lastname: Sze
authors.forename: Pedro A
authors.initials: PA
authors.lastname: Dimitriu
authors.forename: Shizu
authors.initials: S
authors.lastname: Hayashi
authors.forename: W Mark
authors.initials: WM
authors.lastname: Elliott
authors.forename: John E
authors.initials: JE
authors.lastname: McDonough
authors.forename: John V
authors.initials: JV
authors.lastname: Gosselink
authors.forename: Joel
authors.initials: J
authors.lastname: Cooper
authors.forename: Don D
authors.initials: DD
authors.lastname: Sin
authors.forename: William W
authors.initials: WW
authors.lastname: Mohn
authors.forename: James C
authors.initials: JC
authors.lastname: Hogg
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D003550:Cystic Fibrosis / Q000382:microbiology; D004269:DNA, Bacterial / Q000032:analysis; D005260:Female; D006801:Humans; D008168:Lung / Q000382:microbiology*; D008297:Male; D054892:Metagenome; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D025341:Principal Component Analysis; D029424:Pulmonary Disease, Chronic Obstructive / Q000382:microbiology*; D012336:RNA, Ribosomal, 16S; D017422:Sequence Analysis, DNA; D012720:Severity of Illness Index; D012907:Smoking
chemical_list: D004269:DNA, Bacterial; D012336:RNA, Ribosomal, 16S