Oral Diseases and Brain Pathologies: A Systematic Review of Clinical, Neuroimaging, and Mechanistic Evidence

Background. Oral diseases, including periodontitis, dental infections, and oral dysbiosis, have been increasingly associated with systemic conditions. Emerging evidence suggests a potential link between oral health and brain pathologies such as brain abscesses, structural brain damage, and glioma. However, the strength and mechanisms of this oral–brain relationship remain incompletely understood. Objective To systematically review the clinical, neuroimaging, genetic, and mechanistic evidence linking oral diseases with brain outcomes, and to explore the biological pathways underlying this association. Methods A systematic literature search was conducted in PubMed, Scopus, Web of Science, and EBSCO, with additional screening of SciELO, Redalyc, and LILACS. A total of 2,000 records were identified, and 17 studies met the inclusion criteria. Study designs included population-based cohorts, case–control studies, Mendelian randomization analyses, experimental investigations, and narrative or systematic reviews. Data were synthesized narratively following PRISMA guidelines. Risk of bias was assessed using the ROBINS-I tool for observational studies. Results Clinical and epidemiological studies consistently reported a substantial proportion of brain abscesses attributable to odontogenic infections, often associated with clinically silent dental foci. Neuroimaging and Mendelian randomization analyses demonstrated associations between poor oral health and reduced cortical thickness, white matter abnormalities, and markers of brain injury. Experimental studies showed that Porphyromonas gingivalis virulence factors induced IL-6 secretion and PD-L1 upregulation in glioma cells, suggesting immune evasion and tumor progression. Extracellular vesicles derived from periodontal tissues were identified as potential mediators of systemic inflammatory and angiogenic signaling. Conclusions Oral diseases are associated with an increased risk of brain abscess formation, structural brain alterations, and potentially glioma progression. These relationships appear to be mediated by microbial dissemination, chronic inflammation, immune modulation, and extracellular vesicle signaling. Although causality cannot yet be definitively established, oral health represents a modifiable factor with important implications for brain health and neurological disease prevention.