Oral Bacteria Drive Cancer Through Inflammation and DNA Damage Pathways

This review synthesizes current understanding of how oral microbiome dysbiosis contributes to oral cancer pathogenesis, with significant implications for cancer prevention and treatment strategies. Oral squamous cell carcinoma (OSCC) affects over 350,000 people annually worldwide, representing more than 90% of oral cancers.

The research reveals that specific bacterial species, particularly Fusobacterium nucleatum and Porphyromonas gingivalis, are consistently enriched in oral cancer tissues. These periodontal pathogens promote tumorigenesis through multiple molecular mechanisms including activation of pro-inflammatory NF-κB and STAT3 pathways, suppression of apoptosis, and modulation of host immune responses. Additional mechanisms include production of reactive oxygen species and genotoxins, inhibition of tumor suppressors like p53, disruption of cell-cycle regulation, and upregulation of β-catenin signaling.

Crucially, microbiome alterations begin early in the carcinogenic process, appearing in premalignant lesions like oral leukoplakia before cancer develops. This suggests dysbiosis may initiate rather than simply follow malignant transformation. Studies show increased levels of Fusobacterium, Leptotrichia, and Campylobacter in premalignant tissues, with these bacteria producing DNA-damaging toxins and promoting inflammatory environments.

The therapeutic implications are promising. Microbiota-modulating therapies using Lactobacillus probiotics may restore microbial balance, boost immunity, and limit tumor growth. Emerging approaches include engineered bacteriotherapy, microbiome-targeted immunomodulators, and microbiota-based diagnostics that could enable more personalized cancer treatments.

These findings highlight the oral microbiome as both a risk factor and therapeutic target, potentially revolutionizing approaches to oral cancer prevention and treatment through precision microbiome medicine.