The respiratory microbiome: dynamics from health to disease.

Abstract

Research on the respiratory microbiome has moved beyond the sterile-lung paradigm, but disease-associated microbial patterns are still often described as static signatures. In this mini-review, we synthesize current evidence within a dynamic state-transition framework in which respiratory microbial communities are shaped by microbial immigration, elimination, local growth conditions, and host inflammatory tone. This framework traces the respiratory microbiome from early-life assembly and homeostatic maintenance to perturbation, recovery, or persistence in alternative ecological states. We discuss how barrier integrity, mucociliary clearance, mucus and nutrient landscapes, inflammatory feedback, microbial metabolites, and the gut-lung axis regulate microbial stability and disease susceptibility. Across asthma, chronic obstructive pulmonary disease, cystic fibrosis, bronchiectasis, and respiratory infection, dysbiosis is interpreted not as a set of disease-specific taxa, but as a context-dependent outcome of shared ecological mechanisms. We also highlight methodological and translational priorities, including contamination control in low-biomass samples, longitudinal sampling, multi-omics integration, spatial host profiling, and cautious interpretation of association versus causality. Viewing the respiratory microbiome as an ecological system in motion may better connect microbial dynamics with disease heterogeneity, risk stratification, and future microbiome-directed interventions.