From Mouth to Brain: Exploring Oral Microbiome Alterations and Metabolomic Pathways in Glioma Pathophysiology

ABSTRACT Growing evidence highlights a functional link between the oral microbiome and brain tumors, establishing the concept of the “oral–brain axis” in glioma pathophysiology. This review synthesizes current research on how oral microbiota dysbiosis and its associated metabolic signatures influence glioma development, progression, and treatment response. Pathogenic oral bacteria, such as Porphyromonas gingivalis and Fusobacterium nucleatum , are hypothesized to access the central nervous system through several pathways: the disruption of the periodontal barrier (“leaky gums”), compromised blood–brain barriers (“leaky brain”) in high‐grade tumors, and immune‐cell‐mediated transport via the “Trojan horse” mechanism. Distinct oral microbial signatures correlate with glioma grades and molecular subtypes, such as the depletion of Leptotrichia and Capnocytophaga in high‐grade tumors and the enrichment of Bergeyella in IDH1‐mutant gliomas, suggesting the potential for non‐invasive, saliva‐based diagnostics. Furthermore, microbial metabolites, such as short‐chain fatty acids, polyamines, and lipopolysaccharides, may modulate the glioma microenvironment by influencing epigenetic regulation, immune evasion, and tumor metabolism. While the oral microbiome also appears to impact therapeutic outcomes, particularly for immune checkpoint inhibitors, the field is currently limited by a lack of longitudinal human studies. Future research utilizing multi‐omics and causal experimental models is essential to develop microbiome‐informed strategies for glioma diagnosis, prognostication, and therapy.