Topographic heterogeneity of lung microbiota in end-stage idiopathic pulmonary fibrosis: the Microbiome in Lung Explants-2 (MiLEs-2) study

Thorax. 2021 Mar;76(3):239-247. doi: 10.1136/thoraxjnl-2020-214770. Epub 2020 Dec 2.


Background: Lung microbiota profiles in patients with early idiopathic pulmonary fibrosis (IPF) have been associated with disease progression; however, the topographic heterogeneity of lung microbiota and their roles in advanced IPF are unknown.

Methods: We performed a retrospective, case-control study of explanted lung tissue obtained at the time of lung transplantation or rapid autopsy from patients with IPF and other chronic lung diseases (connective tissue disease-associated interstitial lung disease (CTD-ILD), cystic fibrosis (CF), COPD and donor lungs unsuitable for transplant from Center for Organ Recovery and Education (CORE)). We sampled subpleural tissue and airway-based specimens (bronchial washings and airway tissue) and quantified bacterial load and profiled communities by amplification and sequencing of the 16S rRNA gene.

Findings: Explants from 62 patients with IPF, 15 patients with CTD-ILD, 20 patients with CF, 20 patients with COPD and 20 CORE patients were included. Airway-based samples had higher bacterial load compared with distal parenchymal tissue. IPF basilar tissue had much lower bacterial load compared with CF and CORE lungs (p<0.001). No microbial community differences were found between parenchymal tissue samples from different IPF lobes. Dirichlet multinomial models revealed an IPF cluster (29%) with distinct composition, high bacterial load and low alpha diversity, exhibiting higher odds for acute exacerbation or death.

Interpretation: IPF explants had low biomass in the distal parenchyma of all three lobes with higher bacterial load in the airways. The discovery of a distinct subgroup of patients with IPF with higher bacterial load and worse clinical outcomes supports investigation of personalised medicine approaches for microbiome-targeted interventions.

Keywords: bacterial infection; idiopathic pulmonary fibrosis; lung transplantation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Bronchoalveolar Lavage Fluid / microbiology
  • Case-Control Studies
  • Disease Progression
  • Humans
  • Idiopathic Pulmonary Fibrosis / diagnosis
  • Idiopathic Pulmonary Fibrosis / microbiology*
  • Idiopathic Pulmonary Fibrosis / surgery
  • Lung / diagnostic imaging
  • Lung / microbiology*
  • Lung / surgery
  • Lung Transplantation*
  • Microbiota / physiology*
  • Middle Aged
  • Retrospective Studies
  • Tomography, X-Ray Computed / methods*
  • Young Adult