Multi-site microbiomes’ response to chronic obstructive pulmonary disease

ABSTRACT This study aimed to evaluate changes in the oral, nasal, pulmonary, and gut microbiota in patients with chronic obstructive pulmonary disease (COPD) and to explore their interrelationships compared with the healthy group. This study included 33 COPD patients and 29 healthy individuals. A total of 162 oral, nasal, sputum, and fecal samples were obtained. The microbiota was determined using full-length 16S rRNA gene sequencing on the PacBio platform. Alpha diversity was significantly reduced in sputum and fecal samples of COPD patients, while oral and nasal microbiota showed no significant differences. Beta diversity revealed substantial overlap between oral and sputum microbiota in both groups, while nasal and fecal communities were clearly distinct. Linear discriminant analysis effect size analysis identified Haemophilus parahaemolyticus as a sputum biomarker. Source tracking confirmed that the majority of lung microbiota originated from the oral cavity. Interleukin-6 was inversely correlated with short-chain fatty acids (SCFAs)-producing microbiota in fecal samples, suggesting that depletion of these bacteria may contribute to systemic inflammation. Co-occurrence network analysis revealed that the sputum microbial network in COPD patients exhibited reduced robustness and lacked prominent hub nodes. Lung microbiota largely originates from the oral cavity but is changed in COPD. The lung microbiome is still more sensitive and accurate than the oral, nasal, and fecal microbiomes for COPD diagnosis. Fragmented networks in COPD indicate reduced community resilience. IMPORTANCE Lung and gut microbial diversity is significantly reduced in COPD patients. Oral microbiota is the primary source of lung microbes, but poorly predicts COPD status. Haemophilus parahaemolyticus was identified as a novel sputum biomarker in COPD. The bacterial network in COPD lungs is fragmented, lacking the resilience seen in healthy individuals.