Unraveling the Transcriptomic Adaptations of Streptococcus mutans Biofilm to the Post-Biotic Impact of Lactiplantibacillus plantarum

Oral squamous cell carcinoma (OSCC) is a multifactorial disease influenced by microbial dysbiosis and biofilm-induced chronic inflammation. Streptococcus mutans, a principal pathogen, aggravates OSCC by fostering an immunosuppressive tumor microenvironment via biofilm development and virulence-related metabolic alterations. This work investigated the post-biotic effects of Lactiplantibacillus plantarum in reducing S. mutans-related OSCC by obstructing bacterial adhesion, biofilm integrity, and virulence gene expression. GC–MS research revealed that the cell-free supernatant (CFS) of L. plantarum contains the bioactive metabolite 2,4-di-tert-butylphenol (DTP), which demonstrates significant antibacterial and anti-tumor activities. The new antimicrobial peptide Plpl_18 exhibited substantial biofilm inhibition and reduction of bacterial viability. Transcriptomic research indicated that S. mutans 890 treatment with DTP and Plpl_18 downregulated essential biofilm-associated genes (gtfB, gtfC), disturbed carbohydrate metabolism, and initiated a metabolic transition towards lactose utilization. Molecular docking and molecular dynamics simulations (MDS) validated persistent interactions between DTP and Plpl_18 with bacterial virulence factors and OSCC-related proteins (p38, NF-κB), underscoring their therapeutic potential. This research offers innovative perspectives on probiotic biofilm suppression methods and identifies DTP and Plpl_18 as potential options for targeted treatments against S. mutans-induced OSCC. Subsequent investigations into clinical applications may facilitate the development of novel antibacterial interventions and cancer treatment methodologies.