title: Spatial Variation in the Healthy Human Lung Microbiome and the Adapted Island Model of Lung Biogeography.
abstract: BACKGROUND
  The lung microbiome is spatially heterogeneous in advanced airway diseases, but whether it varies spatially in health is unknown. We postulated that the primary determinant of lung microbiome constitution in health is the balance of immigration and elimination of communities from the upper respiratory tract (URT; "adapted island model of lung biogeography"), rather than differences in regional bacterial growth conditions.
  
  
  OBJECTIVE
  To determine if the lung microbiome is spatially varied in healthy adults.
  
  
  METHODS
  Bronchoscopy was performed on 15 healthy subjects. Specimens were sequentially collected in the lingula and right middle lobe (by bronchoalveolar lavage [BAL]), then in the right upper lobe, left upper lobe, and supraglottic space (by protected-specimen brush). Bacterial 16S ribosmal RNA-encoding genes were sequenced using MiSeq (Illumina, San Diego, CA).
  
  
  RESULTS
  There were no significant differences between specimens collected by BAL and protected-specimen brush. Spatially separated intrapulmonary sites, when compared with each other, did not contain consistently distinct microbiota. On average, intrasubject variation was significantly less than intersubject variation (P = 0.00003). By multiple ecologic parameters (community richness, community composition, intersubject variability, and similarity to source community), right upper lobe microbiota more closely resembled those of the URT than did microbiota from more distal sites. As predicted by the adapted island model, community richness decreased with increasing distance from the source community of the URT (P < 0.05).
  
  
  CONCLUSIONS
  In healthy lungs, spatial variation in microbiota within an individual is significantly less than variation across individuals. The lung microbiome in health is more influenced by microbial immigration and elimination (the adapted island model) than by the effects of local growth conditions on bacterial reproduction rates, which are more determinant in advanced lung diseases. BAL of a single lung segment is an acceptable method of sampling the healthy lung microbiome. Clinical trial registered with www.clinicaltrials.gov (NCT02392182).
authors: 1 Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, University of Michigan Medical School, Ann Arbor, Michigan.
authors: Robert P
authors: RP
authors: Dickson
authors: 1 Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, University of Michigan Medical School, Ann Arbor, Michigan.
authors: John R
authors: JR
authors: Erb-Downward
authors: 1 Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, University of Michigan Medical School, Ann Arbor, Michigan.|2 Research Service, Veterans Affairs Ann Arbor Healthcare System, Ann Arbor, Michigan.
authors: Christine M
authors: CM
authors: Freeman
authors: 1 Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, University of Michigan Medical School, Ann Arbor, Michigan.
authors: Lisa
authors: L
authors: McCloskey
authors: 3 Veterans Affairs Eastern Colorado Health Care System, Denver, Colorado.|4 Department of Medicine, Division of Pulmonary Sciences and Critical Care, University of Colorado School of Medicine, Aurora, Colorado.
authors: James M
authors: JM
authors: Beck
authors: 1 Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, University of Michigan Medical School, Ann Arbor, Michigan.|5 Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan; and.
authors: Gary B
authors: GB
authors: Huffnagle
authors: 1 Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, University of Michigan Medical School, Ann Arbor, Michigan.|6 Pulmonary and Critical Care Medicine Section, Medical Service, Veterans Affairs Ann Arbor Healthcare System, Ann Arbor, Michigan.
authors: Jeffrey L
authors: JL
authors: Curtis
mesh_terms: D000328:Adult; D018893:Bronchoalveolar Lavage / Q000379:methods; D001992:Bronchoalveolar Lavage Fluid / Q000382:microbiology*; D001999:Bronchoscopy / Q000379:methods; D004269:DNA, Bacterial / Q000032:analysis; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D008168:Lung / Q000382:microbiology / Q000473:pathology; D008297:Male; D054892:Metagenome / Q000502:physiology*; D064307:Microbiota / Q000502:physiology*; D008875:Middle Aged; D012336:RNA, Ribosomal, 16S / Q000032:analysis; D017422:Sequence Analysis, DNA; D062206:Spatial Analysis
chemical_list: D004269:DNA, Bacterial; D012336:RNA, Ribosomal, 16S
keywords: 16S ribosomal DNA; bronchoscopy; lung; microbiome