A Narrative Review of Airway and Gut Microbiota in Chronic Obstructive Pulmonary Disease: Clinical Associations, Methodological Heterogeneity, and Translational Priorities.

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disorder in which exacerbation susceptibility, persistent inflammation, disease progression, and treatment response are not fully explained by spirometry. Culture-independent studies have associated airway and gut microbial features with clinically relevant COPD phenotypes, but findings are highly sensitive to sampling site, low biomass, contamination control, sequencing depth and platform, bioinformatic workflow, microbial-load quantification, medication exposure, disease state, and host or environmental confounding. Methodological and clinical heterogeneity is therefore a central explanation for inconsistent results. This narrative review, a non-systematic synthesis using a prespecified focused PubMed/MEDLINE search (1 August 2021-1 August 2026), English-language eligibility, single-reviewer selection, structured data charting, and thematic appraisal without formal study-level risk-of-bias grading, evaluates recent human evidence on the airway bacteriome and mycobiome, gut microbiota and metabolites, host-microbe relationships, and the ecological effects of antibiotics and inhaled corticosteroids. Across cohorts, lower airway diversity, states dominated by potential pathobionts (normally resident organisms that may contribute to disease under altered host or ecological conditions), and altered microbial networks are recurrent but not universal associations; no disease-specific taxonomic signature has been validated. Gut microbial and metabolic differences may represent causes, consequences, treatment effects, shared determinants, or combinations of these mechanisms. Relative abundance is difficult to interpret without absolute microbial-load measurement. No microbiota-based diagnostic test, prognostic classifier, or intervention is ready for routine COPD care. Progress requires standardized longitudinal sampling, rigorous controls, absolute quantification, paired airway-gut multi-omics, diverse external validation, and randomized trials with prespecified patient-centered outcomes.