Respiratory Microbiome Remodeling in Aging: Implications for Immunosenescence and Therapeutic Intervention

Source: PubMed Central Open Access, NCBI / U.S. National Library of Medicine

Aging involves progressive declines in lung structure and immune function, increasing the incidence and severity of respiratory diseases and reducing vaccine responsiveness. Meanwhile, the respiratory tract harbors a dynamic microbial ecosystem that contributes to immune homeostasis and colonization resistance. Growing evidence indicates that aging disrupts this host-microbe balance within the respiratory tract; however, the mechanisms and therapeutic implications remain incompletely integrated. This review summarizes age-related remodeling of the respiratory microbiome. Beyond compositional shifts, aging alters microbial functions, including metabolic output and resilience to perturbation, exhibiting downstream effects on epithelial barriers, mucus clearance, and immune priming. Furthermore, as the microbiome-immune axis is modifiable, microbiome-targeted therapies represent key opportunities to restore respiratory homeostasis during aging. These interventions, combined with senescence- and cytokine-directed immunomodulation and vaccine optimization using adjuvants and mucosal immune-informed designs, may reduce infection burden and chronic lung disease progression in older populations. Together, this review highlights that a deeper understanding of age-related respiratory microbiome remodeling and its interplay with immunosenescence will be essential for the rational design of microbiome-informed therapies.