Abstract
BACKGROUND: Airway and gut dysbiosis have been reported in Chronic Obstructive Pulmonary Disease (COPD); however, their relationship and association with clinical features remain poorly understood. We aimed to characterise the lung and gut microbiome in patients with stable COPD and controls. METHODS: Prospective, multicentre, longitudinal and controlled study of n = 60 stable patients with COPD and n = 30 controls. In them, we analysed 16S rRNA-seq in oropharyngeal (OP) swabs, sputum, bronchoalveolar lavage fluid (BALF) and stool. Weighted gene co-expression network analysis (WGCNA) was employed in each sample type to identify modules of co-abundant bacteria associated with clinical traits. FINDINGS: We found that the microbiome in airway and stool samples was highly dissimilar both in patients and controls, with 0.37% of this diversity associated to COPD. The microbiome taxa associated with COPD in OP swabs and sputum were highly similar, but different from BALF, suggesting that OP swabs can be a surrogate sample of sputum. Finally, using WGCNA, we identified: (a) 5 modules in OP swabs and 3 in sputum associated with FEV(1), but some of them were also associated with exacerbations, dyspnoea and inhaled steroid (ICS) use; (b) In BALF 4 modules associated with FEV(1) and dyspnoea, and 2 modules with ICS; and, finally, (c) in stool, 1 module related to FEV(1), 1 to exacerbations and 3 with ICS. INTERPRETATION: The gut and lung microbiomes in patients with COPD are distinct, but both clinically relevant as both present bacterial associations with airflow limitation, exacerbation history, and ICS use. FUNDING: ISC-III PI24/00476. FRPA.2014, ICREA-2024.