Profiling Oral Microbiome Dysbiosis in Premalignant and Malignant Oral Lesions Using 16S rRNA Metagenomic Sequencing in a South-South Nigerian Cohort

The oral microbiome exerts significant influence over local mucosal immunity, inflammatory signaling, and potentially the initiation and progression of oral mucosal malignancies. While microbiome-cancer associations have been explored in Western populations, 16S rRNA-based metagenomic characterization of the oral microbiome in the context of premalignant oral lesions and oral squamous cell carcinoma (OSCC) in sub-Saharan African populations has not been performed. This PhD study characterizes oral microbiome composition and dysbiosis patterns in healthy controls, patients with potentially malignant oral disorders (PMOD: leukoplakia, erythroplakia, and oral submucous fibrosis), and OSCC patients at three tertiary hospitals in Rivers, Edo, and Cross River States in the South South geopolitical zone. Saliva and mucosal swab samples from 45 healthy controls, 45 PMOD patients, and 45 OSCC patients were subjected to 16S rRNA V3-V4 hypervariable region amplicon sequencing using an Illumina MiSeq platform. Bioinformatics analysis including alpha and beta diversity, differential abundance testing, and functional pathway prediction using PICRUSt2 was conducted. Results demonstrate significant progressive dysbiosis from healthy controls through PMOD to OSCC, characterized by depletion of commensal Streptococcus salivarius and enrichment of Fusobacterium nucleatum, Prevotella intermedia, and Treponema denticola in OSCC samples. Metabolic pathway analysis reveals enrichment of lipopolysaccharide biosynthesis pathways in malignant specimens. These findings implicate specific microbial taxa as potential biomarkers of malignant transformation in the South South Nigerian population and open research avenues for microbiome-targeted cancer interception strategies. Keywords: oral microbiome, 16S rRNA sequencing, oral cancer, dysbiosis, South South Nigeria.