Oral Diseases and Brain Pathologies: A Systematic Review with Narrative Synthesis of Clinical, Neuroimaging, and Mechanistic Evidence.

Background: Oral diseases such as periodontitis, dental infections, and oral dysbiosis have been increasingly associated with systemic conditions. Emerging evidence suggests a potential relationship between oral health and neurological disorders, including brain abscesses, structural brain alterations, and gliomas. However, the strength and mechanisms of these associations remain incompletely understood. Objective: To systematically review clinical, neuroimaging, genetic, and mechanistic evidence linking oral diseases with brain pathologies. Methods: A systematic literature search was conducted in PubMed, Scopus, Web of Science, and EBSCO, with complementary screening of SciELO, Redalyc, and LILACS databases. Studies evaluating associations between oral diseases (periodontitis, dental infections, caries, or oral microbiota alterations) and neurological outcomes were considered. Eligible study designs included observational clinical studies, Mendelian randomization analyses, neuroimaging studies, and experimental investigations. Seventeen studies met the inclusion criteria. Due to the substantial heterogeneity in study designs, outcomes, and effect metrics, quantitative meta-analysis was not feasible. Findings were therefore synthesized using a structured narrative approach following PRISMA guidelines. Results: Clinical studies consistently identified odontogenic infections as a relevant source of brain abscesses, frequently originating from chronic or clinically silent dental foci. Neuroimaging and genetic studies reported associations between poor oral health indicators and structural brain alterations, including reduced cortical thickness and white matter abnormalities. Experimental investigations suggested potential biological mechanisms involving microbial dissemination, systemic inflammation, and immune modulation. Virulence factors from Porphyromonas gingivalis have been shown to induce inflammatory signaling pathways and immune checkpoint activation in glioma cells. Conclusions: The current evidence suggests a possible association between oral diseases and several brain pathologies. Although causality cannot be established, the findings highlight the importance of oral health as a potentially modifiable factor relevant to neurological health. Further longitudinal and mechanistic studies are required to clarify these relationships.