Not All Toothpaste Works The Same

Introduction

The oral cavity is one of the most structurally diverse environments in the human body, with a unique microbial ecosystem (i.e., microbiome) consisting of bacteria, fungi, viruses and other groups of microorganisms that inhabit and colonise its various physical niches like teeth, gingiva, inner cheeks and saliva (Reynoso-García et al., 2022). Here, these microbes play a vital role in driving oral health and disease progression, with the majority of bacteria in the oral cavity forming structured microbial biofilms where they carry out functions related to pH regulation, host immune modulation, and nutrient metabolism (Chandra Nayak et al., 2025). 

Some commensal species, like Streptococcus mitis and Veillonella parvula, are also able to further maintain oral homeostasis by executing antagonistic effects that restrict the growth of periodontopathogens like Porphyromonas gingivalis and Tannerella forsythia, and cariogenic (decay-causing) species like Streptococcus mutans (Reynoso-García et al., 2022; Bloch et al., 2024). Colonisation by these bacteria can cause inflammatory tissue destruction that drives the progression of periodontal disease, or the production of acids that erode dental enamel and cause dental cavities (Chandra Nayak et al., 2025).

Beyond diet, smoking, and alcohol consumption, one of the key factors that can drive the growth of these pathogens is lack of adherence to proper hygiene practices. Poor oral hygiene habits, such as inadequate brushing and flossing, can increase risk of oral disease progression by promoting biofilm formation and the proliferation of pathogenic species that can disrupt the composition and functioning of the oral microbial community by pushing it towards dysbiosis (Rajasekaran et al., 2024). Preventative measures to stop this from happening include observation of proper oral hygiene practices and regular use of oral care products like mouthwash, toothpaste, floss string, and interdental brushes to maintain a healthy oral environment that favours the growth of beneficial microbial species over harmful ones (Gallione et al., 2025).

Multiomics (i.e., multiple omics) is an emerging interdisciplinary approach that has permitted a more detailed investigation into the mechanistic mode of action of these oral care products and their overall effect on oral microbial communities. By capturing and integrating data from multiple layers of biological information (e.g., genomics, transcriptomics, proteomics, and metabolomics), multiomics has provided a more comprehensive understanding of product influence over the complex network of interactions underlying these oral microbial communities and host tissues, as well as changes they may induce to the compositional and functional properties of the oral microbiome (Ramji et al., 2025). This improved mechanistic understanding can be used in future to facilitate the development of more efficacious personal care products and individualised, targeted therapeutics for oral care.

Article 1: A randomised, double-blind clinical study into the effect of zinc citrate trihydrate toothpaste on oral plaque microbiome ecology and function (Adams et al., 2025)

This 6-week clinical study aimed to assess the impact of a zinc citrate trihydrate toothpaste (zinc toothpaste) formulation on dental biofilm ecology and function. By using a combined multiomics approach integrating data from metataxonomic, metagenomic, and metatranscriptomic layers, this study looked to provide a detailed analysis of the structural and functional metabolic changes that occur in dental biofilm communities upon exposure to the zinc toothpaste, while also elucidating its mechanism of action and ability to maintain oral hygiene in comparison to a fluoride toothpaste over the course of the study period (Adams et al., 2025).

Results

Species-level community analysis of the collected plaque samples revealed significant differences in community composition between users of the zinc toothpaste and users of a fluoride toothpaste after 6-weeks of consistent product use, with significant shifts in composition observed for the zinc toothpaste that were absent in the fluoride group. Furthermore, significant shifts in the relative abundance of 30 taxa were observed for the zinc toothpaste group, while only 8 were observed for the control toothpaste. 

In the case of the zinc toothpaste, this included an increase in the abundance of groups like Streptococcus and Veillonella, core genera associated with a healthy mouth, and a marked decrease in the abundance of Fusobacterium nucleatum subsp. Polymorphum, an opportunistic oral pathogen whose activity has been linked to the maturation of oral biofilm to facilitate the growth of species associated with inflammation and gum disease. Application of the zinc toothpaste also reduced the amount of Porphyromonas pasteri in the oral cavity, another pathogenic species whose presence has been linked to oral malodour. While the fluoride toothpaste group also displayed changes in some taxa, such as Staphylococcus epidermidis and Haemophilus haemolyticus, these were far more minimal than the zinc toothpaste, demonstrating the ability of zinc-containing toothpastes to more effectively promote growth of beneficial bacteria at the expense of oral pathogens.

Combined metagenomic and metatranscriptomic analyses of these oral microbial communities later found an inhibition of bacterial genes associated with sugar metabolism after zinc toothpaste usage, something that could have implications for reduced production of biofilm metabolites like lactic acid that are damaging to dental enamel. Conversely, an increase in the lysine biosynthesis pathway, a process that has been linked to gum attachment and maintenance, was also observed following use of zinc toothpaste, as well as an increase in nitrogen metabolism and nitrate reduction, which has positive implications for whole-body health, demonstrating the ability of zinc toothpastes to boost genes and metabolic processes associated with good oral health compared to fluoride toothpastes, whose effects on sugar metabolism, lysine biosynthesis, and nitrogen metabolism were far less significant (Adams et al., 2025).

Conclusion

This study was able to successfully demonstrate the beneficial effects of using a zinc-containing toothpaste product on the structure and function of the oral microbiome. Use of this toothpaste was shown to be far more effective in modulating oral health than a traditional fluoride one, with significant shifts in both the composition and metabolic activity of these microbial communities being observed after 8-weeks of use. This included triggering an increase in the abundance of beneficial, protective bacteria like Streptococcus and Veillonella, decrease in the abundance of harmful pathobionts like Fusobacterium, as well as suppressing metabolic pathways could push the oral environment in an unhealthy direction to impede disease progression and pathogen colonisation (Adams et al., 2025). 

Strengths and Limitations of Research

Strengths

Multiomics can also provide a more well-rounded assessment of oral product efficacy during testing by examining their effect on microbiome function in response to product use . This can include elucidating the specific mechanisms by which oral hygiene products or ingredients are able to influence different members of the oral microbiota, while also permitting an improved understanding of significant microbial interactions and their influence over disease modulation and treatment strategies (Adams et al., 2025; Chandra Nayak et al., 2025).

Limitations

The use of dental plaque collection to monitor product effects in many oral multiomics studies can be problematic with regards to the varied composition of bacterial flora at different sites within the oral cavity, and even between surfaces of the same tooth, leading to less precise estimates of community composition at the individual level, and raising issues when tracking compositional shifts over the course of a clinical trial. Collection from predetermined plaque sites can also make it difficult to draw accurate comparisons between healthy and diseased participants, as diseased groups might include samples collected from a mixture of diseased and non-diseased sites (Yama et al., 2023).

Future Directions and Research

Microflora imaging approaches may provide information on spatial distribution and microbial activity within the oral microbiota, with techniques such as fluorescence imaging, mass spectrometry, and Raman spectroscopy, enabling direct visualisation of metabolic substrates (e.g., sugars, amino acids, and nucleic acids) and their chemical activity in response to certain oral care ingredients. This can be used to provide an extra layer of depth when evaluating the efficacy of certain oral care products and therapeutics (Lin et al., 2024).

Conclusion

Multiomics provides an interdisciplinary approach to studying oral health and the microbiome, with research increasingly focusing on the application of these technologies for the development of oral care ingredients and their effects on the microbiome and host oral environment. Certain products and ingredients that have shown potential as effective agents for oral health modulation include stannous compounds and zinc, with such multiomic approaches further paving the way to better understanding their mode of action, as well as their dynamic interplay with oral biomarkers, with many positive implications for product formulations and oral monitoring. However, much work remains to be done to improve the robustness and accuracy of this field of research. Improving these limitations can pave the way for the development of more effective oral care products and treatments for various oral conditions, product testing, and preventative diagnostic therapeutics.

References

Adams, S.E. et al. (2025) ‘A randomised, double-blind clinical study into the effect of zinc citrate trihydrate toothpaste on oral plaque microbiome ecology and function’, Scientific Reports, 15, p. 8136. Available at: https://doi.org/10.1038/s41598-025-92545-0.

Bloch, S. et al. (2024) ‘Oral streptococci: modulators of health and disease’, Frontiers in Cellular and Infection Microbiology, 14, p. 1357631. Available at: https://doi.org/10.3389/fcimb.2024.1357631.

Chandra Nayak, S. et al. (2025) ‘The Oral Microbiome and Systemic Health: Bridging the Gap Between Dentistry and Medicine’, Cureus, 17(2), p. e78918. Available at: https://doi.org/10.7759/cureus.78918.

Gallione, C. et al. (2025) ‘Oral Health Care: A Systematic Review of Clinical Practice Guidelines’, Nursing & Health Sciences, 27(1), p. e70027. Available at: https://doi.org/10.1111/nhs.70027.

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.

Rajasekaran, J.J. et al. (2024) ‘Oral Microbiome: A Review of Its Impact on Oral and Systemic Health’, Microorganisms, 12(9), p. 1797. Available at: https://doi.org/10.3390/microorganisms12091797.

Ramji, N. et al. (2025) ‘Multi-Omics Insights into Gingivitis from a Clinical Trial: Understanding the Role of Bacterial and Host Factors’, Microorganisms, 13(10), p. 2371. Available at: https://doi.org/10.3390/microorganisms13102371.

Reynoso-García, J. et al. (2022) ‘A complete guide to human microbiomes: Body niches, transmission, development, dysbiosis, and restoration’, Frontiers in Systems Biology, 2. Available at: https://doi.org/10.3389/fsysb.2022.951403.

Yama, K. et al. (2023) ‘Dysbiosis of oral microbiome persists after dental treatment-induced remission of periodontal disease and dental caries’, mSystems, 8(5), pp. e00683-23. Available at: https://doi.org/10.1128/msystems.00683-23.