The Oral-Gut-Brain Axis: From Periodontal Dysbiosis to Neuroinflammation-Mechanistic Pathways, Salivary and Intestinal Biomarkers, and Therapeutic Targets: A Narrative Review.

Background: Periodontitis affects approximately 7-11% of the global adult population in its severe forms and has been epidemiologically associated with cardiovascular, cardiometabolic, and neurodegenerative diseases. Low-grade chronic inflammation represents the unifying mechanism; however, an integrative framework connecting the oral cavity, the gut, and the brain into a single mechanistic continuum is lacking. Objective: This narrative review, conducted with structured (but non-systematic) elements and PRISMA-2020 style reporting used solely as a transparency tool, synthesizes current evidence on the oral-gut-brain axis. A comprehensive literature search was conducted in PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar (2000-March 2026), yielding 159 included studies after structured screening and eligibility assessment. The review focuses on: the molecular mechanisms by which periodontal dysbiosis may disrupt intestinal homeostasis and contribute to neuroinflammation; the role of salivary and intestinal biomarkers as monitoring tools for the entire axis; and emerging pharmacological opportunities targeting this tripartite pathway. Results: Periodontal pathogens, particularly Porphyromonas gingivalis (P. gingivalis) and Fusobacterium nucleatum, have been detected ectopically in the gut and are associated with reduced tight junction protein expression and altered Firmicutes/Bacteroidetes ratios in preclinical and observational studies. These perturbations have been associated with increased blood-brain barrier (BBB) permeability, microglial activation, and amyloid-beta (Aβ) accumulation, although causal directionality in humans remains to be established. Salivary biomarkers (MMP-8, IL-1β, IL-6, BDNF) and intestinal biomarkers (short-chain fatty acids, calprotectin) reflect systemic inflammatory burden and offer potential for non-invasive screening. Conclusions: The oral-gut-brain axis provides a plausible unifying framework for understanding comorbidity among periodontal, cardiometabolic, and neurodegenerative diseases; however, current evidence is predominantly associative, and mechanistic extrapolation from preclinical models requires validation in longitudinal human studies. Salivary biomarkers may serve as candidate first-line tools for systemic risk assessment, and pharmacological interventions targeting this axis represent promising investigational directions warranting further clinical evaluation.