COPD bronchial brush microbiome association with lung function and bronchial gene expression

Abstract

Introduction: COPD is related to decline in lung function and microbiome dysbiosis. The relationship between airway bacterial profile with respiratory function and bronchial brush transcriptome in COPD is uncertain. Aim: We sought to investigate the association of COPD bronchial brush microbiome with lung function and bronchial gene expression. Method: Subjects with mild to moderate COPD (n=339) and healthy control individuals (n=207) were recruited as part of the EvA consortium. Spirometry was used to assess the Subjects’ lung function. microbial profile and gene expression from bronchscopic bronchial brush samples were obtained through 16S rRNA gene sequencing and RNAseq respectively. Results: A regression analysis of the postbronchodilator FEV1 % predicted versus bacterial genera abundance revealed Aggregatibacter genus had a significant negative association with respiratory function in COPD samples (r = -5.35; Adjusted p=2.30E-04) and also combined samples from COPD and healthy individuals (r = -2.81; Adjusted p=3.15E-02). Regression analysis of Aggregatibacter abundance versus lung transcriptome revealed four genes (CCL20, PTGS2, IL1B and CF3) with significant positive associations in combined COPD and control samples, however no significant associations were observed between them in either COPD or control samples alone. These genes were involved in IL-17 signalling, TNF signalling, cytokine-cytokine receptor interaction and NF-kappa B signalling pathways. Conclusion: With reduction in the respiratory function, the lung microbiome is associated with increase abundance of Aggregatibacter and up-regulation of pro-inflammatory genes involving in host inflammatory response pathways.