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

Eleanor Valenzi, Haopu Yang, John C. Sembrat, Libing Yang, Spencer Winters, Rachel Nettles, Daniel J. Kass, Shulin Qin, Xiaohong Wang, Michael M. Myerburg, Barbara Methé, Adam Fitch, Jonathan K. Alder, Panayiotis V. Benos, Bryan J. McVerry, Mauricio Rojas, Alison Morris, Georgios D. Kitsios

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)239-247
Number of pages9
JournalThorax
Volume76
Issue number3
DOIs
StatePublished - Mar 1 2021

Keywords

  • bacterial infection
  • idiopathic pulmonary fibrosis
  • lung transplantation

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

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