Metagenomics in Obstructive Lung Diseases: Insights into Microbial Dysbiosis, Host-Microbe Interactions, and the...

Obstructive lung diseases (OLDs), including asthma and chronic obstructive pulmonary disease (COPD), arise from complex interactions among microbial ecosystems, host immunity, metabolic regulation, and environmental exposures. Metagenomic approaches have substantially advanced understanding of these interactions by enabling comprehensive profiling of respiratory and gut-associated microbiomes and their functional potential. Evidence indicates that asthma is frequently associated with early-life microbial perturbations, reduced community diversity, enrichment of Streptococcus, Moraxella, and allergen-associated fungi, and gut dysbiosis that influences immune maturation and tolerance. In contrast, COPD is characterized by adult-onset dysbiosis with Proteobacteria dominance, depletion of commensal anaerobes such as Prevotella and Veillonella, and functional signatures linked to chronic inflammation, xenobiotic metabolism, and exacerbation risk. Across both diseases, alterations in gut microbial composition and metabolite profiles, including short-chain fatty acids, highlight the gut-lung axis as a key regulatory interface shaping airway immune responses. Despite these advances, critical knowledge gaps remain, including limited longitudinal data, incomplete multi-kingdom analyses, and insufficient mechanistic and translational validation of disease-associated microbiome signatures. This review integrates current metagenomic evidence to delineate disease-specific and shared microbial patterns, examines host-microbe interaction pathways within molecular and clinical contexts, and critically evaluates the implications and limitations of microbiome-based interventions. By framing microbiome research within a systems biology and public health perspective, this article underscores the importance of context-dependent interpretation and identifies priorities for future longitudinal, mechanistic, and translational studies in OLDs.