The lung microbiome and asthma: from inflammatory phenotype differentiation to microbe-based immunomodulatory strategies

Abstract

As a complex airway inflammatory disease, the pathogenesis of asthma is closely associated with dynamic changes in the lung microbiome and immune regulation. Asthmatic patients with distinct inflammatory phenotypes exhibit significant alterations in the diversity and dominant microbiota of their lung microbiome, particularly characterized by the colonization of bacteria such as Haemophilus influenzae, Moraxella catarrhalis, and Tropheryma whipplei. The microbial community modulates the differentiation of CD4+ T-cell subsets and activates or inhibits inflammatory pathways, thereby exerting interactive effects on the eosinophilic and neutrophilic inflammatory phenotypes of asthma. Microbial products, such as lipopolysaccharide (LPS), exosomes, and bacterial lysates, play crucial roles in activating or suppressing host immune cells, mediating the initiation and progression of airway inflammation. Current studies have primarily elucidated the mechanisms by which the lung microbiome modulates asthma immune regulation and explored immunomodulatory strategies targeting microorganisms and their products, including the potential of bacterial lysates, probiotic therapy, and microbial exosome therapy in asthma. Unlike previous reviews focusing on the gut–lung axis, this review establishes correspondences between specific bacterial species and distinct asthma endotypes, and critically evaluates the methodological heterogeneity in this field. These reflections provide a theoretical basis for standardizing microbiome research, elucidating microbiota-driven differential progression of asthma subtypes, and advancing microbiome-based precision prevention strategies.