The multifaceted role of oral microbiota-host interactions in oral submucous fibrosis: from pathogenic mechanisms to microecological regulation therapies.

Oral submucous fibrosis (OSF) is a precancerous condition closely associated with areca nut chewing, yet its pathogenesis remains incompletely elucidated. Recent studies have highlighted the critical role of oral microbiota dysbiosis in the progression of OSF. This article systematically reviews alterations in the oral microbiota spectrum associated with OSF, the synergistic pathogenic mechanisms between microbiota and areca nut, core pathways of microbiota-host interactions, and therapeutic strategies based on microbiota modulation. Areca nut chewing modifies the oral microenvironment, suppressing commensal bacteria while enriching pathogens. In OSF patients, pathogenic bacteria such as Fusobacterium nucleatum, Porphyromonas gingivalis, and Candida species are significantly enriched, whereas beneficial bacteria including Lactobacillus and Streptococcus species are reduced. Microbiota dysbiosis promotes fibrogenesis through multiple mechanisms, including disruption of the mucosal epithelial barrier, activation of TLR/NF-κB and NLRP3 inflammatory pathways, induction of Th17/Treg imbalance, interference with tryptophan and short-chain fatty acid metabolism, and exacerbation of oxidative stress. Microbiota-based therapeutic approaches include probiotics, specific targeted antimicrobial peptides, photodynamic therapy, oral microbiota transplantation, and dietary intervention. Future studies should employ multi-omics integrative analyses to establish causality between microbiota dysbiosis and OSF and to advance the clinical translation of precision microbiota-based therapies.