Profiling of human lung and gut microbiomes in different conditions of chronic obstructive pulmonary disease using ontology-based evidence synthesis and reasoning

Chronic Obstructive Pulmonary Disease (COPD) remains one of the leading global causes of morbidity and mortality, with increasing evidence highlighting microbial dysbiosis as a key factor in disease progression and exacerbation. To resolve the inherent heterogeneity in COPD microbiome research, we developed a standardized pipeline termed as Ontology-based Evidence Synthesis and Reasoning (O-ESR), utilizing the Ontology of Host–Microbiome Interactions (OHMI) framework. Our analysis included over 30 studies and identified more than 100 significantly altered bacterial taxa in the human airway and gut microbiomes of human COPD patients across three clinical conditions: COPD versus healthy controls, exacerbation versus stable states, and severe versus moderate diseases. Profiling across taxonomic levels revealed a marked airway expansion of pathogenic genera, including Haemophilus , Moraxella , Pseudomonas , and Burkholderia . Species-level analysis confirmed the specific enrichment of Haemophilus influenzae and Pseudomonas aeruginosa , supporting their roles in airway inflammation and exacerbation susceptibility. In contrast, the gut microbiome of COPD patients exhibited a decrease of beneficial anaerobes involved in short-chain fatty acid (SCFA) production, including Bifidobacterium bifidum , Faecalibacterium prausnitzii , and members of Lachnospiraceae and Ruminococcaceae . Notably, ontology-based reasoning identified a shared depletion of commensal genera such as Prevotella and Veillonella across both anatomical sites and all three clinical conditions, indicating a systemic and progressive loss of microbial diversity. This integrated analysis reveals a COPD-associated microbial landscape characterized by airway Proteobacteria expansion and gut SCFA-producer depletion, suggesting coordinated epithelial dysfunction, immune dysregulation, and gut–lung axis involvement. These findings demonstrate the power of ontological reasoning in decoding complex host-microbiome interactions, providing a robust foundation for microbiome-informed stratification and targeted interventions in COPD management.