RNA interference and its regulatory role in oral biofilm formation and pathogenicity

Objective: This systematic review examines how RNA-based regulatory mechanisms modulate host–microbe interactions, particularly focusing on how RNA molecules, extracellular vesicle–associated RNA cargo, transcriptional responses, and host genetic polymorphisms influence the development, persistence, and pathogenicity of oral biofilms.Materials and Methods: Thirty-four original research articles were selected from a predefined database. Studies were screened using PRISMA guidelines, and only experimental work involving RNA regulation, RNA-bearing extracellular vesicles, transcriptomics, or host genetic susceptibility were included. Narrative synthesis was adopted due to methodological heterogeneity across models such as epithelial cultures, animal models, transcriptomic platforms, and microbial biofilm systems.Results: Strong evidence indicates that RNA-mediated processes contribute critically to host responses against oral biofilms. Streptococcus mutans and Porphyromonas gingivalis produce extracellular vesicles containing RNA cargo that modulates epithelial barrier pathways, inflammatory cytokine expression, and innate immune gene signatures. Host genetic polymorphisms in IL-1β, MMPs, FOXP3, and other immune-regulatory genes influence susceptibility to biofilm-associated disease. Transcriptomic studies reveal that epithelial cells and periodontal ligament stem cells undergo significant RNA-level remodeling when exposed to pathogenic biofilms, especially under nutrient or iron-limited conditions. These host RNA responses influence tissue resilience, inflammation intensity, and disease progression.Conclusion: RNA-associated regulatory mechanisms are central to the host’s reaction to oral biofilms and significantly influence pathogenicity, inflammation, barrier dysfunction, and susceptibility to periodontal or peri-implant disease. Understanding cross-kingdom RNA signaling—particularly EV-RNA and host transcriptional regulation—may uncover new diagnostics and targeted RNA-based therapies for oral infectious diseases.