Topographic Heterogeneity of Lung Microbiota in End-Stage Idiopathic Pulmonary Fibrosis: The Microbiome in Lung Explants-2 (MiLEs-2) Study

Abstract

AbstractBackgroundLung 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.MethodsWe sampled subpleural tissue from up to three lobes as well as airway-based specimens (bronchial washings and airway tissue) in patients with IPF, connective tissue disease-associated interstitial lung disease (CTD-ILD), cystic fibrosis (CF), and chronic obstructive pulmonary disease (COPD) and donor lungs deemed unsuitable for transplant (controls). We quantified bacterial load and profiled communities by polymerase chain reaction (PCR) amplification and sequencing of the 16S rRNA gene.FindingsExplants from 62 IPF, 15 CTD-ILD, 20 CF, 20 COPD and 20 control patients were included. Airway-based samples had higher bacterial load compared to distal parenchymal tissue across all patient groups. IPF basilar tissue had much lower bacterial load compared to CF and control lungs (p<0.001). Among patients with IPF, no differences in microbial community profiles were found between parenchymal tissue samples from different lobes. With Dirichlet multinomial models, a cluster of IPF patients (29%) with distinct composition, high bacterial load and low alpha diversity was identified, exhibiting higher odds for acute exacerbation of IPF or death.InterpretationIPF explants exhibited low biomass in the distal parenchyma of all three lobes with higher bacterial load in the airways. The discovery of a distinct subgroup of IPF patients with higher bacterial load and worse clinical outcomes supports investigation of personalized medicine approaches for microbiome-targeted interventions.Key MessagesWhat is the key question?Bronchoalveolar lavage microbiome profiles in early idiopathic pulmonary fibrosis (IPF) have been associated with disease progression, but the regional heterogeneity of resident microbiota in end-stage IPF has not been defined.What is the bottom line?IPF explants demonstrate higher bacterial load in airway compared to parenchymal samples, but no differences in between apical or basilar parenchymal samples. A subgroup of patients with higher bacterial load and respiratory pathogen abundance was associated with worse clinical outcomes.Why read on?Patient-specific heterogeneity in the lung microbiome of IPF supports the need for personalized microbiome-targeted interventions in IPF.