title: Host-Microbial Interactions in Idiopathic Pulmonary Fibrosis.
abstract: Changes in the respiratory microbiome are associated with disease progression in idiopathic pulmonary fibrosis (IPF). The role of the host response to the respiratory microbiome remains unknown.
  
  
  
  To explore the host-microbial interactions in IPF.
  
  
  
  Sixty patients diagnosed with IPF were prospectively enrolled together with 20 matched control subjects. Subjects underwent bronchoalveolar lavage (BAL), and peripheral whole blood was collected into PAXgene tubes for all subjects at baseline. For subjects with IPF, additional samples were taken at 1, 3, and 6 months and (if alive) 1 year. Gene expression profiles were generated using Affymetrix Human Gene 1.1 ST arrays.
  
  
  
  By network analysis of gene expression data, we identified two gene modules that strongly associated with a diagnosis of IPF, BAL bacterial burden (determined by 16S quantitative polymerase chain reaction), and specific microbial operational taxonomic units, as well as with lavage and peripheral blood neutrophilia. Genes within these modules that are involved in the host defense response include NLRC4, PGLYRP1, MMP9, and DEFA4. The modules also contain two genes encoding specific antimicrobial peptides (SLPI and CAMP). Many of these particular transcripts were associated with survival and showed longitudinal overexpression in subjects experiencing disease progression, further strengthening the relationship of the transcripts with disease.
  
  
  
  Integrated analysis of the host transcriptome and microbial signatures demonstrated an apparent host response to the presence of an altered or more abundant microbiome. These responses remained elevated in longitudinal follow-up, suggesting that the bacterial communities of the lower airways may act as persistent stimuli for repetitive alveolar injury in IPF.
authors.affiliation: 1 National Heart and Lung Institute, Imperial College London, London, United Kingdom.|2 Royal Brompton Hospital, London, United Kingdom; and.
authors.forename: Philip L
authors.initials: PL
authors.lastname: Molyneaux
authors.affiliation: 1 National Heart and Lung Institute, Imperial College London, London, United Kingdom.
authors.forename: Saffron A G
authors.initials: SAG
authors.lastname: Willis-Owen
authors.affiliation: 1 National Heart and Lung Institute, Imperial College London, London, United Kingdom.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Cox
authors.affiliation: 1 National Heart and Lung Institute, Imperial College London, London, United Kingdom.
authors.forename: Phillip
authors.initials: P
authors.lastname: James
authors.affiliation: 1 National Heart and Lung Institute, Imperial College London, London, United Kingdom.|2 Royal Brompton Hospital, London, United Kingdom; and.
authors.forename: Steven
authors.initials: S
authors.lastname: Cowman
authors.affiliation: 1 National Heart and Lung Institute, Imperial College London, London, United Kingdom.|2 Royal Brompton Hospital, London, United Kingdom; and.
authors.forename: Michael
authors.initials: M
authors.lastname: Loebinger
authors.affiliation: 3 Fibrosis Discovery Performance Unit, GlaxoSmithKline R&D, GlaxoSmithKline Medicines Research Centre, Stevenage, United Kingdom.
authors.forename: Andrew
authors.initials: A
authors.lastname: Blanchard
authors.affiliation: 3 Fibrosis Discovery Performance Unit, GlaxoSmithKline R&D, GlaxoSmithKline Medicines Research Centre, Stevenage, United Kingdom.
authors.forename: Lindsay M
authors.initials: LM
authors.lastname: Edwards
authors.affiliation: 1 National Heart and Lung Institute, Imperial College London, London, United Kingdom.|2 Royal Brompton Hospital, London, United Kingdom; and.
authors.forename: Carmel
authors.initials: C
authors.lastname: Stock
authors.affiliation: 1 National Heart and Lung Institute, Imperial College London, London, United Kingdom.|2 Royal Brompton Hospital, London, United Kingdom; and.
authors.forename: Cécile
authors.initials: C
authors.lastname: Daccord
authors.affiliation: 1 National Heart and Lung Institute, Imperial College London, London, United Kingdom.|2 Royal Brompton Hospital, London, United Kingdom; and.
authors.forename: Elisabetta A
authors.initials: EA
authors.lastname: Renzoni
authors.affiliation: 2 Royal Brompton Hospital, London, United Kingdom; and.
authors.forename: Athol U
authors.initials: AU
authors.lastname: Wells
authors.affiliation: 1 National Heart and Lung Institute, Imperial College London, London, United Kingdom.
authors.forename: Miriam F
authors.initials: MF
authors.lastname: Moffatt
authors.affiliation: 1 National Heart and Lung Institute, Imperial College London, London, United Kingdom.|2 Royal Brompton Hospital, London, United Kingdom; and.
authors.forename: William O C
authors.initials: WOC
authors.lastname: Cookson
authors.affiliation: 1 National Heart and Lung Institute, Imperial College London, London, United Kingdom.|2 Royal Brompton Hospital, London, United Kingdom; and.
authors.forename: Toby M
authors.initials: TM
authors.lastname: Maher
mesh_terms: D000368:Aged; D001992:Bronchoalveolar Lavage Fluid / Q000382:microbiology; D005260:Female; D005500:Follow-Up Studies; D054884:Host-Pathogen Interactions; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000378:metabolism* / Q000382:microbiology*; D008297:Male; D064307:Microbiota; D011446:Prospective Studies; D059467:Transcriptome
keywords: acute lung injury; expression; idiopathic pulmonary fibrosis; microbiome; usual interstitial pneumonia