Gut microbiota dysbiosis in COPD patients increases the level of queuine in the blood serum abnormally enhancing the viability of lung epithelial cells.

Introduction: To investigate the association between gut-airway microbiota dysbiosis, serum queuine levels, and early malignant transformation in patients with chronic obstructive pulmonary disease (COPD). We further explored whether the potential mechanistic role of queuine in enhancing lung epithelial cell viability under cigarette smoke exposure. Methods: Stable COPD patients were stratified into a high relative abundance of Proteobacteria group (CH) and a low relative abundance of Proteobacteria group (CL) using 16S rRNA gene sequencing of fecal samples. Airway microbiota profiles were analyzed in parallel to assess gut-lung axis coupling. Serum queuine concentrations were quantified using LC-MS/MS in healthy controls, COPD subgroups (CL and CH), and COPD patients complicated by lung cancer. Clinical symptoms (CAT, mMRC, SCSS) and spirometry (FEV Results: The α-diversity of gut microbiota did not differ between CH and CL. In contrast, β-diversity showed separation (PERMANOVA P = 0.062), with CH characterized by Proteobacteria enrichment and relative depletion of Firmicutes, Bacteroidota, and Actinobacteriota. Airway communities showed concordant remodeling with shifts in taxa consistent with dysbiosis. Serum queuine concentrations increased stepwise from healthy controls to COPD, were higher in CH than CL, and were highest in COPD complicated by lung cancer. Despite comparable pulmonary function and symptom scores between CH and CL groups, the CH group exhibited a significantly higher number of pulmonary nodules on CT imaging, particularly ground-glass nodules. Conclusion: COPD-associated gut microbiota dysbiosis, particularly enrichment of Proteobacteria, is closely associated with elevated systemic queuine levels. Excess queuine enhances cell viability of smoke-exposed lung cancer epithelial cells and is associated with increased pulmonary nodules