Lung microbiome dysbiosis is associated with mortality in COPD

Introduction: COPD is a heterogenous disease which makes identifying patients more likely to respond to a particular treatment or at higher risk of poor clinical outcomes challenging. Methods: Microbiome characterization by 16S bacterial rRNA gene sequencing was performed on sputum samples obtained from 297 COPD patients studied during stable disease with a median follow up of 4 years. Samples were classified at the phyla level as proteobacteria or firmicutes dominant whilst at the genera level samples were classed as Haemophilus or Streptococcus dominant. If no phyla or genera was represented at greater than 40% these were classed as “balanced microbiomes”. The results were compared to clinical characteristics to determine the utility of stable disease microbiome in predicting outcomes. Results: Proteobacteria dysbiosis and loss of microbiota diversity (Shannon-Wiener Diversity Index) was associated with more severe COPD by GOLD stage (P=0.0007), more frequent prior exacerbations (P=0.0057), low blood eosinophil counts ( Proteobacteria dysbiosis was associated with an increased risk of mortality (HR 2.39 95% CI 1.23-4.66, p=0.01) compared to those with a balanced or firmicutes dominated microbiome. Uniquely among Firmicutes, patients with a Streptococcus dominated microbiome had an increased mortality risk (HR 2.58 95% CI 1.03-6.46, p= 0.043) when compared to those with balanced microbiomes. Conclusions: Reduced microbiome diversity, driven by Proteobacteria (predominantly Haemophilus) or Streptococcus dysbiosis is associated with increased mortality and may indicate COPD endotypes at increased risk of negative outcomes. Funder: GSK