From Periodontal Pocket to Systemic Diseases: Mechanistic Insights Into the Role of Porphyromonas gingivalis in Host Pathology.

Porphyromonas gingivalis (P. gingivalis), a keystone pathogen in periodontitis, has been increasingly recognised as a mechanistic bridge linking periodontal infection to pathological destruction in distant organs. P. gingivalis virulence factors, including gingipains, lipopolysaccharides (LPS), and outer membrane vesicles (OMVs), mediate complex host-pathogen interactions. In this review, we critically evaluated recent experimental studies which demonstrate the effects of P. gingivalis oral infection on systemic diseases, including cardiovascular disease (CVD), diabetes mellitus (DM), adverse pregnancy outcomes (APOs), colorectal cancer (CRC), and Alzheimer's disease (AD). In CVD, DM, and AD, P. gingivalis gingipains exert proteolytic activity that disrupts key cellular targets, including endothelial adhesion molecules, insulin receptors in insulin-responsive tissues, and neuronal proteins. In AD, P. gingivalis LPS contributes to neuronal damage by inducing tau hyperphosphorylation and synaptic dysfunction. In APO and AD, P. gingivalis OMVs play a central role in compromising barrier integrity. These processes converge on five principal pathogenic pathways: (1) barrier and structural disruption, (2) immune activation and subversion, (3) mitochondrial dysfunction and oxidative stress induction, (4) systemic inflammation, and (5) metabolism-mediated effects. Understanding these shared pathways underscores the importance of controlling periodontal disease in promoting systemic health.