Human oropharyngeal resistome of COPD cases and controls using ResCap

Background: Livestock-related emissions have been associated with aggravations of respiratory symptoms in patients with chronic obstructive pulmonary disease (COPD), potentially by altering the respiratory resistome. Objectives: This study investigates the structure of the acquired oropharyngeal (OP) resistome of patients with COPD and controls, its interplay with the respiratory microbiome and associations with residential livestock exposure. Methods: In a matched case-control study in the rural Netherlands, we analysed OP swabs from 35 patients with COPD and 34 controls, none of whom had used antibiotics in the preceding 4 weeks. Resistome profiling was performed using ResCap, complemented by prior characterization of the microbiome via 16S rRNA-based sequencing. Residential livestock farm exposure was defined using distance-based variables alongside modelled concentrations of livestock-emitted microbial pollutants. We compared resistome profiles between patients with COPD and controls, examining alpha and beta diversity as well as differential abundance. Additionally, we assessed the interplay between the resistome and microbiome using co-occurrence networks and Procrustes analysis. Variations in resistome profiles were also analysed based on residential livestock exposures. Results: Patients with COPD exhibited higher resistome diversity than controls (Shannon diversity, P = 0.047), though resistome composition remained similar between groups (PERMANOVA, P = 0.19). Significant correlations were observed between the OP resistome and microbiome compositions, with distinct patterns in co-occurrence networks. Residential exposure to livestock farms was not associated with resistome alterations. Conclusions: Our findings reveal the COPD airway as a hospitable environment for antimicrobial resistance genes, irrespective of recent antimicrobial usage. Demonstrating the interplay between the resistome and microbiome, our study underscores the importance of a deeper understanding of the resistome in respiratory health.