Lung Microbiota Contribute to Pulmonary Inflammation and Disease Progression in Pulmonary Fibrosis.

American Journal of Respiratory and Critical Care Medicine
David N O'DwyerRobert P Dickson

Abstract

Rationale: Idiopathic pulmonary fibrosis (IPF) causes considerable global morbidity and mortality, and its mechanisms of disease progression are poorly understood. Recent observational studies have reported associations between lung dysbiosis, mortality, and altered host defense gene expression, supporting a role for lung microbiota in IPF. However, the causal significance of altered lung microbiota in disease progression is undetermined. Objectives: To examine the effect of microbiota on local alveolar inflammation and disease progression using both animal models and human subjects with IPF. Methods: For human studies, we characterized lung microbiota in BAL fluid from 68 patients with IPF. For animal modeling, we used a murine model of pulmonary fibrosis in conventional and germ-free mice. Lung bacteria were characterized using 16S rRNA gene sequencing with novel techniques optimized for low-biomass sample load. Microbiota were correlated with alveolar inflammation, measures of pulmonary fibrosis, and disease progression. Measurements and Main Results: Disruption of the lung microbiome predicts disease progression, correlates with local host inflammation, and participates in disease progression. In patients with IPF, lung bac...Continue Reading

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Methods Mentioned

BETA
Flow Cytometry
Assay
PCR
PCA
ELISA
amplicon sequencing

Clinical Trials Mentioned

NCT01071707

Software Mentioned

R
COMET
Prism
R vegan package
R Core Team
PERMANOVA
R : A Language and Environment for Statistical Computing
R Foundation for Statistical Computing
GraphPad

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