Synergistic inhibition of Streptococcus mutans biofilms by fluoride and epigallocatechin gallate: Insights from multi-omics analysis

Yuanyuan Chen^*Tiantian WuLong Jiang^*Junjun Zhao^*

• Shanghai Ninth Peoples Hospital, Shanghai, China

Introduction: Streptococcus mutans biofilms are central to the development of dental caries, and strategies that effectively attenuate biofilm formation remain essential for disease control. This study examined the combined antibiofilm effects of sodium fluoride (NaF) and epigallocatechin gallate (EGCG), a green tea–derived polyphenol, and delineated the underlying mechanisms using an integrative multi-omics framework. Materials and Methods: Synergistic interactions between NaF and EGCG were first assessed by crystal violet staining and checkerboard microdilution analysis. Biofilm biomass, viability, and matrix composition were quantified using colony-forming unit assays, scanning electron microscopy, confocal laser scanning microscopy, and measurements of water-insoluble extracellular polysaccharides. Transcriptomic, proteomic, and metabolomic profiling were carried out to identify perturbed pathways, and arginine levels were quantified to evaluate metabolic responses. Results: Co-treatment with NaF and EGCG produced a synergistic inhibitory effect, markedly reducing biomass, viable cells, and extracellular polysaccharide content. Microscopic analyses demonstrated disrupted microcolony organization and compromised matrix architecture. Multi-omics profiling revealed concentration-dependent alterations in amino acid, carbohydrate metabolism, nucleotide and energy-related processes. Conclusions: NaF and EGCG synergistically disrupt S. mutans biofilms by simultaneously impairing extracellular polysaccharide synthesis, redox balance, and central metabolic activity. These findings support the potential of combining EGCG with fluoride to enhance caries prevention strategies.