From Bleeding Gums to Brilliant Smiles

Introduction 

The oral cavity supports complex microbial communities that play a crucial role in both oral and systemic health. When this balance is disrupted, it can lead to conditions such as gingivitis and periodontitis. Certain species, particularly Porphyromonas gingivalis, act as pathogens that promote disease progression even at low abundance. Oral biofilm development follows a structured sequence, beginning with early colonizers such as Streptococcus, which alter local conditions and enable later colonization by more pathogenic bacteria like Fusobacterium nucleatum. These shifts create anaerobic environments that support inflammation, tissue damage, and tooth loss. Increasing evidence also links periodontal disease to systemic conditions, including cardiovascular disease, diabetes, neurodegenerative disorders, and chronic kidney disease, largely through persistent inflammation and the spread of bacterial components into the bloodstream (Ramji et al., 2025).

To better understand these complex interactions, multi-omics approaches, integrating genomic, transcriptomic, proteomic, and metabolomic data, are increasingly being applied to oral health research. These methods have revealed associations between microbial composition, host responses, and disease progression, while also enabling the identification of biomarkers in oral fluids and tissues (Ramji et al., 2025). Together, they provide a more comprehensive framework for evaluating disease mechanisms and guiding the development of targeted, evidence-based oral care interventions 

Article: Multi-Omics Insights into Gingivitis from a Clinical Trial: Understanding the Role of Bacterial and Host Factors (Ramji et al., 2025)

Using a multiomics approach combining salivary proteomics with microbial composition analysis, this 8-week study sought to investigate the effects of a stannous fluoride-containing toothpaste on oral microbiome composition, and host biomarker responses, in a cohort of patients divided into individuals with (high bleeders) or without (low bleeder) gingivitis to better understand the both molecular mechanisms by which this ingredient is able to influence microbiome structure and function, and its interactions with host tissues of the oral cavity, with particular emphasis on the supragingival region (Ramji et al., 2025).

Results

Significant differences were observed between high and low bleeders at baseline, with the former possessing a greater abundance of bacterial genera associated with gingivitis, like Porphyromonas, Fusobacterium, and Alloprevotella that were positively correlated with clinical measures like gingival inflammation and bleeding. However, after 4-weeks of stannous fluoride-containing toothpaste use, changes in the abundance of 17 bacterial genera were recorded. Compositional shifts that involved a significant decrease in the relative abundance of Porphyromonas, and significant increase in the relative abundance of commensal genera such as Rothia and Haemophilus, aligned with improved clinical signs like decreased bleeding and inflammation. These observations point to stannous fluoride as an effective treatment for unhealthy gingival microbiomes, where it works to promote growth of beneficial bacteria over pathogens, which could, in turn, reduce symptoms associated with gingivitis, like inflammation and oxidative stress.

Proteomic analysis of saliva samples at baseline revealed a total of 192 host proteins displaying differential expression between the high and low bleeder group. Further enrichment analysis of these proteins showed biological processes such as tissue homeostasis and antimicrobial defence responses were downregulated in the high bleeders, rendering the oral cavity more susceptible to pathogen colonisation and impairing healing. On the other hand, processes related to immune system activity, response to stress, inflammatory response, and response to oxidative stress were upregulated, with this combination of processes possibly working to induce a dysregulated, pro-inflammatory oral environment that facilitates tissue destruction and disease progression.

Of these 192 proteins, 71 were identified as host proteomic disease biomarkers of gingivitis. However, following 8-weeks of treatment with the stannous fluoride toothpaste, 29 of the proteins showed treatment-induced shifts from disease towards a healthier state. Other groups of proteins with improved expression included 69 (of the 192) proteins involved in antimicrobial responses, cell stress responses, and immune system processes that were downregulated after treatment, thus demonstrating the ability of stannous treatments to modulate immune activity, and reduce inflammation within the host oral environment to support improved tissue health and resilience.

Collagen breakdown is a process associated with clinical markers like bleeding and gingival inflammation, as was observed at significantly higher proportions in the high-bleeder group than the low bleeder one. However, consistent use of the stannous fluoride toothpaste over the 8-week trial period was enough to result in a significant reduction in oral collagen breakdown and associated clinical markers in high bleeders. This result may be attributed to stannous fluoride’s ability to inhibit the activity of bacterial collagenase enzymes in pathobionts like F. nucleatum and P. gingivalis, which work to degrade host collagen tissue in the gingival region to cause physiological effects such as sagging, thus promoting preservation of oral tissue integrity (Ramji et al., 2025).

Conclusion

Using an integrated multiomics approach, this study was able to provide a comprehensive overview of how a stannous fluoride toothpaste treatment can positively influence microbial community structure and metabolite profiles by reducing abundance of pathogenic bacteria, like Porphyromonas and Fusobacterium, and promoting growth of beneficial commensals such as Rothia and Haemophilus in individuals exhibiting clinical signs of gingivitis. These changes are also associated with reductions in the expression of disease biomarkers and proteins involved in processes like inflammation, oxidative stress, and tissue damage, while simultaneously improving the structural integrity of oral tissues that occur as a result of collagen breakdown (Ramji et al., 2025).

Strengths and Limitations of Research

Strengths

The use of multiomics approaches to examine the complex interplay between the microbiome, oral environment, and associated metabolites, can be used to facilitate the identification of specific microbial and metabolic biomarkers that can be used to monitor and track changes in oral health, paving the way for preventive care measures as well as informing the development of targeted therapeutic approaches with improved individual biocompatibility and minimal side effects to mitigate against disease-related changes (Ramji et al., 2025).

Limitations

There are still very few multiomics studies available looking at the effects of oral care products on oral health as there is a relatively new focus on this type of research. As a result, our understanding of their effects on microbiome function remain limited, making it difficult to draw absolute conclusions regarding the effectiveness of certain products or oral care ingredients at promoting a healthy microbial community composition and function.

Future Directions and Research

Future integration of multiomics technologies (e.g., genomic, transcriptomic, proteomic, and metabolomic data) systems biology, and synthetic biology may work to more effectively draw a link between microbial genes and different natural products, essentially allowing prediction of metabolites derived from the single microbe or community level, and facilitating the discovery of novel active molecules that can be used to drive product formulation for both cosmetic and therapeutic oral applications (Wu et al., 2024). 

Conclusion

Together, advances in multi-omics research are transforming how oral health is understood and managed by revealing the complex interactions between microbial communities, host biology, and clinical outcomes. By moving beyond surface-level observations to capture functional and molecular changes, this approach provides a more precise framework for evaluating oral care ingredients, identifying important biomarkers, and supporting evidence-based product development. As this field continues to evolve, integrated biological insights will be essential for designing targeted, effective oral care solutions that promote long-term health, resilience, and disease prevention.

References

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.

Wu, S. et al. (2024) ‘Multi-omic analysis tools for microbial metabolites prediction’, Briefings in Bioinformatics, 25(4), p. bbae264. Available at: https://doi.org/10.1093/bib/bbae264.