Oral Mucosal Microbiome as A Factor in The Progression of Leukoplakia in Patients with Carbohydrate Metabolism Disorders

Abstract

Leukoplakia of the oral mucosa in patients with carbohydrate metabolism disorders exhibits a heightened propensity for epithelial dysplasia, with a clinically and molecularly substantiated increase in malignant potential. This progression correlates with shifts in the structure and function of the mucosal microbiome, which acts as a pathophysiological cofactor in epithelial instability. In type 2 diabetes mellitus, metabolic dysregulation contributes to chronic mucosal hypoxia, endothelial dysfunction, and oxidative stress, establishing a microenvironment favorable for dysbiosis. Targeted studies demonstrate increased colonization by opportunistic taxa including Porphyromonas gingivalis, Fusobacterium nucleatum, and Candida albicans, organisms implicated in pro-inflammatory signaling, epithelial–mesenchymal transition, and disruption of intercellular adhesion. The presence of hyperkeratotic or erosive leukoplakic lesions in ventral oral regions corresponds with elevated levels of microbial virulence factors, epithelial proliferation indices (Ki-67), and p53 pathway activation. These findings support the concept of a microbially modulated oncogenic niche within metabolically compromised mucosa. Integrating microbial profiling into the diagnostic algorithm for oral leukoplakia may enhance prognostic precision and inform preventive strategies in high-risk diabetic populations.