Salivary Biomarkers: A New Horizon in Clinical Dentistry

Saliva, often referred to as the “mirror of the body,” is a remarkably complex and valuable biofluid that holds a wealth of information about an individual’s health, disease status, and well-being. Saliva originates from diverse glands within the oral cavity, comprising a rich and intricate assortment of biological molecules. These include a wide range of proteins, enzymes, hormones, nucleic acids like DNA and RNA, as well as metabolites crucial for biological processes.^1,2 Alongside these complex constituents, saliva can also harbour contaminants such as bacteria, epithelial cells, gingival crevicular fluid, and residual food particles.³ This amalgamation of both essential compounds and potential contaminants renders saliva a dynamic and informative biofluid with immense potential for medical, dental, and diagnostic applications.

Significance of salivary biomarkers in the detection of oral diseases:

Salivary biomarkers have emerged as valuable indicators for the early detection and monitoring of various oral diseases. This non-invasive approach offers insights into the intricate biochemical and molecular changes within the oral cavity. Biomarkers such as C-reactive protein (CRP), matrix metalloproteinases (MMPs), interleukins (ILs), salivary enzymes, oral microbiota profiles, cytokines, and immunoglobulins have shown promise in revealing underlying pathological processes, inflammation, microbial imbalances, and tissue damage associated with conditions like periodontal disease, dental caries, and oral cancers. (Table 1) In addition to these biomarkers, changes in the population, activity, or functional status of oral neutrophils can serve as early indicators of oral health issues. For instance, alterations in neutrophil counts or their responsiveness to infections may signify underlying oral inflammatory conditions, including periodontal diseases.⁴ By harnessing the diagnostic power of these salivary biomarkers, early intervention and tailored treatment strategies can be employed to mitigate the impact of oral diseases on both oral and systemic health.

Table 1: List of salivary biomarkers significant for oral health

Specific	Non-specific	Inflammatory	Emerging Markers
Immunoglobulins (IgA, IgG & IgM) Salivary enzymes (lysozymes, peroxidase, α-amylase, proteinase) Salivary ions (Calcium, bicarbonate, chloride, fluoride)	Proteins (Mucin, lactoferrins, histatin, fibronectin, cystatins) Growth factors [Epidermal growth factor (EGF), Vascular endothelial growth factor (VEGF)] Epithelial keratins Hormones (Cortisol, Inflammatory cells (Oral neutrophils) Bacteria (Streptococus species and Actinomyces. viscous.)	Matrix-metalloproteinase [MMP-8, MMP-9, MMP-13] Interleukin [IL1 (IL1α & IL1β), IL4, IL6, and IL8] Cytokines Tumor Necrosis Factor (TNF-α) Osteocalcin Osteopontin Telopeptide Neutrophils	Salivary proteome Salivary transcriptome

Salivary biomarkers and dental caries: Salivary biomarkers have emerged as promising tools for the detection and personalized monitoring of dental caries, a prevalent oral health issue. Key biomarkers such as Streptococcus mutans and Lactobacilli levels provide insights into the microbial environment, aiding in assessing caries risk.⁵ Additionally, increased salivary enzymatic biomarkers, including alpha-amylase, proteinase-3 and carbonic anhydrase (CA VI), correlate with increased caries occurrence.^6,7 pH levels and buffering capacity of saliva indicate susceptibility to acid erosion.⁸ By leveraging these biomarkers, clinicians can identify early stages of caries development and tailor interventions to individuals. This facilitates the implementation of focused preventive strategies, leading to enhanced outcomes in oral health.

Salivary biomarkers, periodontal diseases, and peri-implantitis: Salivary biomarkers play a significant role in the context of periodontal diseases, offering insights into disease detection, progression, and treatment monitoring. IL-1ß, IL-6, MMP-8, and MIP-1 alpha have been identified as potential markers for distinguishing between health, gingivitis, and periodontitis,⁹ with IL-1ß, MMP-8, IL-6, and haemoglobin showing the highest sensitivity values for periodontitis detection in a recent meta-analysis.¹⁰ These biomarkers can help in assessing the severity of periodontal disease, predicting disease progression, and evaluating the response to treatment. Additionally, the convergence of salivary biomarkers with bacterial analysis holds promise, as periodontopathic bacteria detection mirrors subgingival plaque sampling.¹¹ A combined approach of bacterial and host-derived biomarkers yielded information about the oral microbiota composition, aiding in understanding microbial imbalances associated with periodontitis.¹² To date, a definitive and compelling biomarker for the diagnosis of periodontitis has not yet been identified.

Currently, limited research addresses salivary biomarkers in periimplantitis; nevertheless, certain proteinases and cytokines have emerged as potential diagnostic or monitoring tools for this condition. MMP-8 concentrations exhibited elevation in saliva or peri-implant crevicular fluid,^13,14 particularly notable in patients with concurrent periodontitis.¹⁵ A similar trend was noticed in patients with cardiovascular diseases, where MMP-8 functioned as a point-of-care biomarker.¹⁶

Salivary biomarkers and oral cancers: Oral cancer presents a growing global concern with increasing incidence and mortality rates, necessitating advanced screening and early detection strategies. Specific and sensitive biomarkers are essential for effective screening, diagnosis, and monitoring of this malignancy. Unlike deeper cancers, the oral location of oral cancer enables direct contact between saliva and the lesions, making salivary biomarker measurement a promising alternative to traditional methods. Saliva contains DNA, RNA, and protein molecules from cancer cells, offering a non-invasive means of obtaining diagnostic information.¹⁷ Utilizing post-genomic technologies, altered gene and protein expressions in oral cancer patients’ saliva can be assessed, holding the potential for early diagnosis, prognosis, and treatment monitoring.¹⁸The emerging field of salivary biomarkers demonstrates significant clinical promise in the fight against oral cancer.

Conclusion

Salivary biomarkers have emerged as transformative tools in dental practice, offering non-invasive insights into an individual’s oral and systemic health. Comprising a diverse array of molecules, saliva provides a dynamic snapshot of health status. These biomarkers hold significant diagnostic potential for oral diseases like dental caries and periodontal conditions. Moreover, their role extends to oral cancer detection, enabling timely intervention. Integrating salivary biomarkers into routine practice has the potential to revolutionize dental care, fostering tailored approaches and improved patient outcomes through precision diagnostics and targeted therapie.

Oral Health welcomes this original article.

Conflict of Interest: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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About the Authors

Dr. Madhura Tandale has a Bachelor of Dental Surgery (BDS) with two years of clinical practice from Mumbai, MH, India. She has graduated from McGill University with an MSc in Dental Science.

Dr. Radhika Chhibber has a Bachelor of Dental Surgery (BDS) with a year of clinical practice from India. She has graduated from McGill University with an MSc in Dental Science with a research focus on pediatric periodontal health.

Dr. Haider Al-Waeli is a certified Periodontist, a Fellow of the Royal College of Dentists of Canada and works as an Assistant Professor at the Faculty of Dentistry at Dalhousie University. Dr. Haider Al-Waeli received a Ph.D from McGill University and a Master in Periodontics from Dalhousie.