Prevotella genera abundance in bronchial brush samples differentiates COPD from health and is associated with gene expression

Abstract

Background: COPD is associated with airway inflammation and bacterial dysbiosis. The relationship between the airway microbiome and bronchial gene expression in COPD is poorly understood. Aim: We sought to determine differences in the airway microbiome from bronchial brushings in COPD and health and to investigate whether these distinguishing bacteria are related to bronchial gene expression. Methods: Subjects with mild-to-moderate COPD (n=339) or controls (n=207) were recruited as part of the EvA consortium from 9 centres. Microbial profile and gene expression from bronchscopic bronchial brush samples were obtained through 16S rRNA gene sequencing and RNAseq respectively. Results: Prevotella was the bacterial genera that most strongly distinguished COPD (Median proportion [95% CI] 0.28 [0.25 to 0.3]) from health (0.4 [0.36 to 0.44] ; p=2.7E-10). A regression analysis of the lung transcriptional signal from bronchial brushings versus Prevotella abundance in combined case and control samples revealed 64 genes which had significant associations that met false discovery rate criteria (35 positive and 29 negative) after correction for age, disease state, gender and centre. No significant associations were observed between gene expression and Prevotella abundance in the COPD and healthy subjects alone. Conclusion: Prevotella best discriminated the bronchial microbiome between COPD and health and was associated bronchial gene expression. Whether these genes might reveal mechanistic pathways that are a consequence or a cause of the altered microbiome in COPD needs to be further investigated.