The Gut Mycobiome and Inter-kingdom Microbial Networks are linked to COPD Severity in Lung Cancer Patients

Chronic obstructive pulmonary disease (COPD) is increasingly recognized as a systemic disorder affecting host–microbiome interactions beyond the airways. Although bacterial alterations in COPD have been documented, the gut mycobiome and its ecological integration with bacterial communities remain unexplored. In this study, we profiled the gut mycobiome of 61 non-small-cell lung cancer (NSCLC) patients stratified by COPD severity using ITS2 sequencing and analyzed 47 overlapping patients with available metagenomic data to construct cross-kingdom bacterial–fungal networks. Alpha diversity, assessed by Shannon, Simpson, and Chao1 indices, did not differ significantly between patients with and without severe COPD. Partial least squares discriminant analysis (PLS-DA) revealed partial separation of the two groups, with COPD severity explaining 6% of overall compositional variance (R²=0.06, p = 0.058). COPD-severe patients exhibited a significantly reduced Ascomycota/Basidiomycota ratio (p = 0.039) and lower relative abundance of Mucoromycota. Analysis of compositions of microbiomes (ANCOM) identified Myrothecium and Lasiodiplodia crassispora enriched in severe COPD, while Helotiales_unclassified and Phallus atrovolvatus were more abundant in non-severe cases. Fungal co-occurrence networks demonstrated reduced connectivity and modularity in severe COPD (28 nodes, 39 edges) compared with non-severe COPD (33 nodes, 64 edges). Cross-kingdom analyses integrating bacterial genera revealed strengthened Candida–Enterococcus/Clostridium hubs and weakened Faecalibacterium/Roseburia–yeast associations in severe disease. Keystone analysis showed increased centrality for Candida, Aspergillus, Enterococcus, and Clostridium, and decreased centrality for Akkermansia and Roseburia. A compositional balance classifier achieved high discriminatory power (AUC = 0.88) in distinguishing COPD-severe from non-severe patients. These findings indicate that COPD severity is not characterized by major diversity loss but by guild-specific compositional shifts and extensive network rewiring, favoring oxygen-tolerant, opportunistic taxa over short-chain fatty acid–associated commensals.