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

Аннотация

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. Keywords: Oral leukoplakia; dysbiosis; oral mucosal microbiome; epithelial dysplasia; type 2 diabetes mellitus; Porphyromonas gingivalis; Fusobacterium nucleatum; Candida albicans; oxidative stress; p53; Ki-67; MMP-9; carcinogenic risk; metabolic comorbidity; epithelial remodeling. epithelial barrier function, and alter cellular turnover. These conditions coincide with structural and Introduction: Leukoplakia of the oral mucosa compositional changes in the mucosal microbiome, demonstrates variable malignant potential, modulated characterized by increased colonization of anaerobic by systemic metabolic states and local epithelial- and opportunistic species. Taxa such as microbial interactions. In patients with carbohydrate Porphyromonas gingivalis, Fusobacterium nucleatum, metabolism disorders, particularly type 2 diabetes and Candida albicans have been identified at higher mellitus, the prevalence of dysplastic and relative abundance in leukoplakic tissues of hyperproliferative lesions is increased. These lesions metabolically dysregulated individuals. These frequently exhibit verrucous or erosive morphology organisms express virulence factors capable of and are preferentially located in anatomically modulating epithelial proliferation, apoptosis susceptible regions such as the ventral tongue and floor resistance, and extracellular matrix degradation. of the mouth. Molecular profiles of leukoplakic epithelium in this Chronic hyperglycemia and associated cohort often reveal elevated Ki-67 indices, p53 microangiopathy induce tissue hypoxia, impair stabilization, and increased MMP-9 activity, indicating International Journal of Medical Sciences And Clinical Research 43 https://theusajournals.com/index.php/ijmscr International Journal of Medical Sciences And Clinical Research (ISSN: 2771-2265) a shift toward a pro-oncogenic phenotype. The spatial enzymatic degradation of intercellular junctions [Zhou, correlation between microbial biofilm formation and Microbiome Shifts in Oral Precancer, 2020]. zones of epithelial atypia suggests direct microbial Quantitative PCR and in situ hybridization consistently involvement in the promotion of genomic instability detect higher bacterial loads in high-risk anatomical and disruption of cellular homeostasis. Despite the sites such as the ventrolateral tongue and floor of the clinical significance, the role of the mucosal mouth [Sridharan, Anatomical Distribution of High-Risk microbiome as a determinant of leukoplakia Microbiota, 2021]. progression in metabolic pathology remains The integration of microbiome profiling with insufficiently characterized. This study investigates the immunohistochemical markers (p16, Ki-67, MMP-9) compositional and functional attributes of the oral provides a composite risk model for identifying microbiome in leukoplakia patients with carbohydrate leukoplakia with malignant potential in metabolically metabolism disorders, with the aim of identifying compromised individuals [Hernandez, Microbial microbiota-associated markers of epithelial Predictors of Oral Carcinogenesis, 2022]. However, transformation risk. microbiota-based diagnostics in routine screening The progression of oral leukoplakia in patients with protocols remain underdeveloped despite growing carbohydrate metabolism disorders is accompanied by evidence of predictive microbial signatures structural and immunological alterations in the [Warnakulasuriya, WHO Classification of Oral mucosal barrier, closely linked to microbial dysbiosis. Precancer, 2022]. Metabolic impairment in type 2 diabetes mellitus METHODS contr