Role of Oral-Lung Infection Axis on Respiratory Health

High-throughput metagenomic sequencing and advances in mucosal immunology have refuted the traditional physiological concept of a sterile respiratory tract. The oral cavity has been recognized as a dynamic determinant of systemic health. As in other parts of the body, recent studies also suggest that pulmonary health may be linked to oral health. Under eubiotic conditions, the oral microbiome maintains local immunological homeostasis and colonization resistance. Oral dysbiosis, characterized by sequential shifts in microbial communities and the proliferation of the pathogenic red complex (Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia), induces a state of chronic systemic inflammation, potentially involved in an infectious axis between the oral cavity and the lung. This review evaluates the tripartite systemic pathways of metastatic infection, metastatic injury, and metastatic inflammation that govern the translocation of oral pathobionts and their bioactive components, including lipopolysaccharides, outer membrane vesicles, and matrix metalloproteinases, to the lower respiratory tract via microaspiration and hematogenous circulation. The clinical implications across the chronic respiratory disease spectrum are examined, with a focus on how deficits in oral microbial diversity influence chronic obstructive pulmonary disease (COPD) pathogenesis, modulate the pulmonary virome and mycobiome, and stimulate maladaptive trained immunity. Furthermore, the contribution of biological aging is assessed, highlighting the roles of immunosenescence, inflammaging, and physiological reflex decline within the broader mucosal continuum. Finally, the clinical translation of this axis is analyzed, emphasizing the integration of saliva-based point-of-care nano-theranostics, metatranscriptomic profiling, and targeted interventions-such as professional oral biofilm management in intensive care settings and precision microbiome engineering-to preserve respiratory function and restore immune homeostasis.