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

**Authors:** Yuanyuan Chen, Tiantian Wu, Long Jiang, Junjun Zhao

PMC · DOI: 10.3389/fmicb.2026.1766833 · Frontiers in Microbiology · 2026-02-19

## TL;DR

This study shows that combining fluoride and a green tea compound effectively disrupts harmful dental biofilms through multiple biological mechanisms.

## Contribution

The study reveals the synergistic antibiofilm mechanism of fluoride and EGCG using multi-omics analysis in Streptococcus mutans.

## Key findings

- Co-treatment with NaF and EGCG significantly reduced biofilm biomass and viable cells.
- Multi-omics analysis showed disrupted amino acid, carbohydrate, and energy metabolism pathways.
- Microscopic analysis revealed compromised biofilm matrix and microcolony organization.

## Abstract

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.

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.

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.

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.

## Linked entities

- **Chemicals:** sodium fluoride (PubChem CID 5235), epigallocatechin gallate (PubChem CID 1287)
- **Diseases:** dental caries (MONDO:0005276)
- **Species:** Streptococcus mutans (taxon 1309)

## Full-text entities

- **Genes:** glucosyltransferases [NCBI Gene 1028270], SloR [NCBI Gene 1029759], enolase [NCBI Gene 1028540], glycosyltransferase [NCBI Gene 1029496], beta-D-fructosyltransferase [NCBI Gene 1029219], CitG [NCBI Gene 1028349]
- **Diseases:** Dental caries (MESH:D003731), LC (MESH:D009800), infectious condition (MESH:D003141), EPS (MESH:C564877), pain (MESH:D010146)
- **Chemicals:** Alexa Fluor 647 (MESH:C569686), SYTO9 (MESH:C103389), fosfructose (MESH:C029063), proton (MESH:D011522), crystal violet (MESH:D005840), anthrone (MESH:C004522), homogentisic acid (MESH:D006713), D-ribose-1,5-bisphosphate (-), carbohydrate (MESH:D002241), fructan (MESH:D005630), arginine (MESH:D001120), 2-amino-1-methyl-6-phenyl-imidazo[4,5-b]pyridine (MESH:C049584), hydroxyapatite (MESH:D017886), phenylalanine (MESH:D010649), Ribose-5-phosphate (MESH:C031626), amino acid (MESH:D000596), shikimate (MESH:C000723335), 4-hydroxycinnamic acid (MESH:C495469), purine (MESH:C030985), sucrose (MESH:D013395), Lipid (MESH:D008055), CO2 (MESH:D002245), phenylpyruvate (MESH:C031606), O-succinylhomoserine (MESH:C014196), polyphenol (MESH:D059808), folate (MESH:D005492), calcium (MESH:D002118), DMSO (MESH:D004121), pyridoxamine (MESH:D011733), glucose (MESH:D005947), phosphocholine (MESH:D010767), pyridoxal-phosphate (MESH:D011732), dihydroxyacetone phosphate (MESH:D004099), tryptophan (MESH:D014364), NAD+ (MESH:D009243), PBS (MESH:D007854), vitamin B6 (MESH:D025101), beta-lactam (MESH:D047090), glutaraldehyde (MESH:D005976), aromatic amino-acid (MESH:D024322), 4-pyridoxate (MESH:D011735), zinc (MESH:D015032), PI (MESH:D010716), phosphate (MESH:D010710), fluorapatite (MESH:C025105), gold (MESH:D006046), benzo[a]pyrene (MESH:D001564), methanol (MESH:D000432), EGCG (MESH:C045651), succinic acid (MESH:D019802), 4-hydroxyphenylpyruvic acid (MESH:C010590), glucan (MESH:D005936), carbon (MESH:D002244), N2 (MESH:D009584), histidine (MESH:D006639), 2,5-dihydroxybenzaldehyde (MESH:C112784), polysaccharide (MESH:D011134), 4-nitrosobiphenyl (MESH:C072328), Fluoride (MESH:D005459), catechin (MESH:D002392)
- **Species:** Homo sapiens (human, species) [taxon 9606], Streptococcus mutans (species) [taxon 1309], Streptococcus mutans UA159 (strain) [taxon 210007], Nicotiana tabacum (American tobacco, species) [taxon 4097]
- **Cell lines:** ATCC 700610 — Homo sapiens (Human), Lung adenocarcinoma, Cancer cell line (CVCL_0023)

## Full text

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## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12960562/full.md

## References

55 references — full list in the complete paper: https://tomesphere.com/paper/PMC12960562/full.md

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Source: https://tomesphere.com/paper/PMC12960562