From Surface Cleaning to Precision Care

Introduction

Periodontal disease arises from a disruption of the normal bacterial balance in the oral cavity, leading to chronic inflammation of the gingiva and, in advanced cases, irreversible damage to the supporting tissues of the teeth. Gingivitis, the early and reversible stage, affects a large proportion of adults worldwide and can progress to periodontitis if left unmanaged. Globally, periodontal disease represents a significant public health burden, contributing to disability, reduced quality of life, and substantial economic costs. Its development is closely linked to the accumulation of mature dental biofilms driven by inadequate oral hygiene, which promotes the overgrowth of pathogenic bacteria. Species such as Porphyromonas gingivalis, Tannerella forsythia, Fusobacterium nucleatum, Prevotella species, and Actinomyces are consistently associated with disease onset and progression (Hu et al., 2024).

Given the central role of bacterial dysbiosis in periodontal disease, oral care products have been developed to target plaque accumulation and inflammation using ingredients with antimicrobial or modulatory properties, such as chlorhexidine, cetylpyridinium chloride, stannous fluoride, zinc salts, hydrogen peroxide, and prebiotic agents like arginine. While some of these ingredients demonstrate clear clinical benefits, particularly for gingivitis control, their precise effects on bacterial function and virulence remain incompletely understood. Emerging transcriptomic research suggests that different ingredients can selectively alter bacterial gene expression, influencing metabolic pathways, stress responses, and virulence-related mechanisms. A deeper understanding of how specific oral care ingredients affect pathogenic bacteria at the molecular level is therefore essential for the rational design of more effective formulations (Hu et al., 2024).

Article: The Effect of Oral Care Product Ingredients on Oral Pathogenic Bacteria Transcriptomics Through RNA-Seq (Hu et al., 2024)

The gene expression activity of six representative periodontal pathogenic bacteria: Actinomyces viscosus, Streptococcus mutans, Porphyromonas gingivalis, Tannerella forsythia, Fusobacterium nucleatum, and Prevotella pallens was measured using RNA sequencing (RNA-Seq) following exposure to nine common ingredients found in toothpaste and mouthwash, these being: stannous fluoride, stannous chloride, arginine bicarbonate, cetylpyridinium chloride, sodium monofluorophosphate, sodium fluoride, potassium nitrate, zinc phosphate, and hydrogen peroxide. This allows for an improved understanding of how individual oral care ingredients are able to influence bacterial activity, and allows for assessment of the effectiveness of each ingredient against the six bacterial species (Hu et al., 2024).

Results

Analysis of the different treatments revealed stannous fluoride, stannous chloride, and hydrogen peroxide to have the most significant effects in reducing bacterial gene expression, with stannous chloride and hydrogen peroxide being among the most potent ingredients for inhibiting gene expression in all tested bacteria, and cetylpyridinium chloride reducing expression in almost all bacteria, with the exception of F. nucleatum. Inhibition of gene expression was significantly greater in the group receiving treatment with these ingredients compared to the no-treatment control group, indicating the effectiveness of these compounds in restricting bacterial growth and activity. 

Transcriptomic analysis of bacterial gene expression found significant inhibition of the lipopolysaccharide (LPS) biosynthesis pathway in response to stannous chloride, stannous fluoride, and cetylpyridinium chloride use, with LPS molecules involved in bacterial cell membrane formation where they can act to trigger inflammation, tissue destruction, and bone loss associated with gingivitis and periodontal disease. These results indicate an ability of these compounds to work to downregulate bacterial genes associated with this pathway, and further restrict pathogen growth. Gene expression analysis also revealed a significant downregulation of infection-related genes in response to sodium fluoride, stannous chloride, and stannous fluoride, which has the effect of also reducing the virulence of the different bacteria.

Bacterial degradation enzymes involved in the breakdown of host tissues and proteins to trigger inflammation and periodontal disease were also investigated via gene expression analysis. Results indicated a downregulation of these genes, particularly in response to stannous compounds, cetylpyridinium chloride, and sodium fluoride, with enzymes like hemolysin, which plays a role in red blood cell destruction and tissue damage, and collagenase, which allows bacteria to penetrate connective tissue and induce inflammation being significantly inhibited in response to these ingredients (Hu et al., 2024).

Conclusion

The results of this study provide strong evidence to suggest the application of certain oral care product ingredients can significantly disrupt or alter the transcriptomic and metabolic activity of a variety of oral periodontopathogenic bacteria, with compounds like stannous fluoride, stannous chloride, and cetylpyridinium chloride being the most potent and players in triggering gene expression changes that lead to the inhibited growth and pathogenic activity of these bacteria, thus reducing their overall virulence and ability to trigger changes in the physical oral environment that induce progression of periodontal disease (Hu et al., 2024).

Strengths and Limitations of Research

Strengths

Allows for a more holistic discernment of how different chemical treatments can influence biological function by providing a community-wide perspective of how different microorganisms can respond to individual chemicals within oral care products rather than focusing on a single species or set of genes. By providing such a mechanistic understanding of these chemicals’ modes of action, it can allow for screening and ranking of ingredients for more efficient product formulations, as well as identifying compounds that hit different targets or different pathogens, further guiding product design (Hu et al., 2024).

Limitations

Many of these studies still rely on 16S rRNA sequencing as a way to classify and determine compositional properties of the oral microbiome instead of high-throughput methods like shotgun metagenomic sequencing, limiting the resolution with which these microbial groups can be identified, and restricting the depth of functional gene analysis and exploration that can be achieved. This, therefore, limits the level of functional characterisation of oral biofilms that can be achieved using omics approaches (Xie et al., 2025).

Future Directions and Research

Single-cell sequencing technologies can be implemented alongside existing multiomics approaches to enable the study of less abundant species of bacteria present within oral biofilms, as well as enabling targeted isolation and investigation of individual cell behaviors within complex microbial communities. This can provide further insight into health-disease markers associated with specific strains, and allow characterisation of the ecological profiles of previously unknown oral microbes and their response to various oral care products/formulations (Lin et al., 2024).

Conclusion

Periodontal disease reflects a complex interplay between pathogenic bacteria, host responses, and environmental influences, with dysregulated microbial activity driving inflammation and tissue destruction. Growing evidence shows that oral care ingredients can influence not only bacterial survival but also key molecular pathways linked to virulence, immune activation, and tissue degradation. By modulating bacterial gene expression involved in processes such as endotoxin production, host tissue breakdown, and infection-related mechanisms, targeted formulations have the potential to reduce pathogenicity. Advancing molecular and multi-omics approaches offers a valuable framework for understanding these interactions at greater depth, supporting the development of more precise oral care strategies that better preserve oral health and help prevent disease progression.

References

Hu, P. et al. (2024) ‘The Effect of Oral Care Product Ingredients on Oral Pathogenic Bacteria Transcriptomics Through RNA-Seq’, Microorganisms, 12(12), p. 2668. Available at: https://doi.org/10.3390/microorganisms12122668.

Lin, Y. et al. (2024) ‘Omics for deciphering oral microecology’, International Journal of Oral Science, 16(1), p. 2. Available at: https://doi.org/10.1038/s41368-023-00264-x.

Xie, Q. et al. (2025) ‘Comprehensive Analysis of Orthodontic Treatment Effects on the Oral

Microbiome, Metabolome, and Associated Health Indicators’, International Dental Journal, 75(3), pp. 1585–1598. Available at: https://doi.org/10.1016/j.identj.2025.02.014.