A systematic review and meta-analysis reveals enrichment of pro-inflammatory and bacterial immunity-modulating taxa in oral squamous cell carcinoma

Abstract

Introduction Oral squamous cell carcinoma (OSCC) is a major concern due to high recurrence, therapeutic resistance, and mortality. Increasing evidence indicates that oral microbiome dysbiosis contributes to OSCC development, yet comprehensive multi-cohort evaluations are limited. A systematic review and meta-analysis of the oral microbiome was conducted to identify conserved taxa in patients with OSCC. Methods A systematic review and meta-analysis was conducted according to PRISMA guidelines, using data from PubMed, Embase, Web of Science, and Google Scholar. Raw 16S rDNA sequences were processed in QIIME 2 (v2024.10) for quality control, taxonomic classification, and diversity analysis. Linear Discriminant Analysis Effect Size (LEfSe) analyses and machine learning were used for the identification of conserved taxa. Results Significant microbial shifts were observed between OSCC and healthy groups. OSCC samples showed enrichment of taxa, which further identified as conserved taxa such as Porphyromonas, Fusobacterium, Campylobacter, Catonella, Prevotella, Selenomonas, and Veillonella, with species including Campylobacter showae, Capnocytophaga granulosa, Capnocytophaga leadbetteri, Prevotella loescheii, Streptococcus anginosus, Streptococcus pneumoniae, and Treponema medium. Healthy individuals exhibited higher levels of Actinobacillus, Corynebacterium, Escherichia-Shigella, and Haemophilus, particularly H. parainfluenzae, Rothia aeria, R. dentocariosa, and Selenomonas spp. Bray–Curtis beta-diversity analysis confirmed significant compositional differences between groups. Sample type and geography-based comparisons revealed additional variation: Geographically, Lautropia and Haemophilus were common across regions, whereas Cutibacterium, Escherichia-Shigella, Gracilibacteria, and several species appeared specific to India. Functional predictions revealed enrichment of pathways related to environmental and genetic information processing, as well as cellular processes in OSCC. Notably, significant enrichment of genes involved in inflammation, ABC transporters, and bacterial immunity was observed in OSCC groups. Conclusion Overall, this study demonstrates the enrichment of microbial taxa associated with chronic inflammation and carcinogenesis, along with a depletion of protective commensal microbes in patients with OSCC. These findings highlight distinct taxonomic and functional microbiome signatures associated with OSCC and emphasize the influence of sample type and geography on oral microbial composition. The enrichment of predicted inflammatory genes, transport-associated genes, and bacterial immune-related genes suggests the potential contribution of microbial communities to chronic inflammation and tumor progression.