Why the COPD Microbiome Matters: How Airway Microbes Shape Disease Severity and Treatment Response

Background: Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease caused by multiple factors, with diverse clinical manifestations leading to varying treatment outcomes. Dysbiosis of the respiratory microbiome is one of the key contributors to this variability. Objective and Methods: Due to differences in microbial detection technologies and sample collection methods, studies on the characteristics of respiratory prokaryotic microbiota and how these microbes influence host functions in COPD patients have yielded variable results. In this review, we conducted a comprehensive search of relevant literature from PubMed, ScienceDirect, and Elsevier, summarizing studies on the characteristics and functional analyses of prokaryotic microbiota under various technical approaches. The goal was to identify common patterns of microbiota changes in COPD across different disease states, as well as individual microbial influences on host functions. Results: Compared with healthy adults, in stable-phase COPD patients, the relative abundance of Prevotella species in the Bacteroidetes phylum is significantly reduced. During acute exacerbations, the predominant microbiota is composed of Moraxella, Haemophilus , and Streptococcus species from the Proteobacteria and Firmicutes phyla. Clinical indicators in COPD patients are correlated with the abundance of Streptococcus (Firmicutes) and Prevotella (Bacteroidetes) species. Furthermore, the different phyla of respiratory prokaryotic microbiota are associated with innate immunity, metabolism, and inflammation factors related to COPD. Conclusion: This review summarizes evidence on dynamic changes in the airway prokaryotic microbiome during COPD progression. It highlights the dual role of these microbial changes as biomarkers of disease progression and modifiable targets for personalized care. Observed patterns—such as reduced Prevotella abundance in stable disease and the dominance of Moraxella, Haemophilus , and Streptococcus during acute exacerbations—provide a basis for stratifying patients and designing individualized treatment plans. Microbiome analysis may aid in early identification of high-risk patients for preventive strategies, guide pathogen-specific antimicrobial or immunomodulatory therapy, and allow treatment response to be monitored through microbial shifts. By linking distinct microbial profiles to host immune and inflammatory pathways, this approach supports the development of tailored interventions to restore microbial balance. These strategies could improve clinical outcomes and advance precision medicine in COPD management. Keywords: chronic obstructive pulmonary disease, COPD, airway microbiome, prokaryotic microorganisms, dysbiosis, disease endotype, microbial composition, airway inflammation, host-microbiome interaction