Understanding the field of dysbiosis and host- microbe interactions requires expanding our understanding beyond specific pathogens. The role of beneficial bacterial species and how they interact with each other is crucial (6). Host biomarkers also play a very important role on oral ecology, such as receptors for microbiome metabolites, lipid mediators of inflammation, chemokines, cytokines, enzymes, and other proteins. Exploring protein biomarkers not only provides insights into the pathogenic processes but also establishes the groundwork for precision medicine (6).

As previously mentioned, precision medicine demands a comprehensive system approach to integrate multi-level data in the search for accurate and reliable biomarkers of disease activity and novel therapeutic targets, with the aim to improve the management of chronic conditions across all medical domains (6). Biomarkers, measurable substances, serve as valuable data resources for indicating physiological health, screening pathological processes, and assessing responses to therapeutic intervention (6).

Numerous studies were carried out to analyze the relationships between saliva composition and oral diseases including periodontitis (7–10), carious lesions (11), and oral cancer (12, 13). These studies have shown that any shift in oral microbial biofilm and subsequent inflammatory response are reflected in saliva. As a result, saliva has been proposed as a potential medium for disease detection (7), even during early pathogenic changes prior irreversible tissue damage (14). Furthermore, saliva analysis has shown promises in monitoring disease progression (15) and evaluating responses to treatment strategies (15). Utilizing saliva as a diagnostic medium exerts several advantages; its collection is simple and painless, enabling for large quantities to be obtained without posing complications for the patients. Additionally, saliva demonstrates high durability (16).

Within the context of periodontitis, a nuanced understanding reveals three distinct phases: inflammation, connective tissue degradation, and bone resorption. Throughout each phase, the identification of specific biomarkers serves as a diagnostic compass, providing a comprehensive understanding of the patient's current stage of pathologic breakdown (17). The traditional diagnostic methods solely often fail to accurately reflect current disease activity and to identify high risk individuals (18). Hence, the meticulous monitoring of biomarkers stands as a pivotal element, emphasizing the significance of preliminary testing to inform the selection of supplementation dosage and duration. A recent systematic review highlights several biomarkers, including macrophage inflammatory protein-1 alpha (MIP-1α), IL-1β, IL-6, and MMP-8 (matrix metalloproteainase-8), as promising indicators for diagnosing periodontitis (19). Integrating clinical measures with assessments of pathogen and cytokines levels can yield a diagnostic sensitivity of up to 74% for predicting periodontitis progression (20). Future studies should focus on determining the optimal combination of biomarkers that would allow for the early diagnosis of periodontitis, as well as those that could be used to monitor treatment or serve as endpoints for treatments.

Salivary biomarkers can be an effective tool also in detecting caries in earlier stages and assessing a patient's caries risk. These biomarkers include nitrite, nitrate, immunoglobulin A, mucin, histatin and proline- rich proteins. A recent systematic review has demonstrated that nitrite levels in saliva serve as a reliable biomarker for dental caries in children (21). However, further research in this area is necessary. Additionally, the application of Artificial Intelligence (AI) could enhance the capability of salivary biomarkers to accurately diagnose and manage several oral diseases, including caries and periodontitis (22).

Over the past decades, there has been a growing recognition of the bidirectional connection between oral health, particularly periodontal health, and overall systemic health. This has led to a heightened awareness among physicians regarding the significance of prioritizing oral health alongside systemic health, given that oral cavity serves as a significant reservoir of microorganisms (23). Special high-risk groups emphasize the interplay between oral and systemic health. The suggested mechanisms that facilitate the connection between oral and systemic health involve predisposing and precipitating factors. These encompass genetic elements like gene polymorphisms, environmental influences such as stress and habits like smoking, and dietary choices featuring high-fat or heavily processed foods. Furthermore, medications, microbial dysbiosis, bacteremia, and changes in the host immune response contribute to mediating this relationship (24).

Specifically, periodontitis and periodontal pathogens have been associated with diabetes mellitus, metabolic syndrome, obesity, eating disorders, liver disease, cardiovascular disease, Alzheimer disease, rheumatoid arthritis, adverse pregnancy outcomes, and cancer (24–26).

The importance of nutrition and its role in contributing to periodontal disease has been already described (41–43). While a balanced diet is crucial for maintaining periodontal health particularly, it is also essential for optimal tissue repair and immune function before and after periodontal procedures. Supplementation of specific nutrients that could be lacking may be necessary. Therefore, emphasis is placed on nutritional supplements for ensuring optimal regenerative treatment (44, 45). The supplemented nutrients and their role in oral health are summarized in Table 1.

Generally, personalized medicine not only concentrates on the recognition of associations between systemic diseases and contributing factors but also aims to tailor treatments based on an individual's unique characteristics and preferences. Therefore, by involving patients in decision- making discussions regarding medical approaches, clinicians acknowledge the importance of autonomy to make decisions about their healthcare and highlight the effects on their well- being. Furthermore, patients often rely on information from different sources when being confronted with unfamiliar problems. By providing support during the decision- making processes, clinical staff have the opportunity to be transparent about the complexity of the medical situations and inform the patients about genetic testing, biomarkers, treatment options, and potential risks or benefits. This allows the engagement in discussions resulting in a clear understanding of potential treatment options and the implementation of lifestyle modifications and required habit changes. Throughout this process, clinicians are able to address associated uncertainties and promote trust in patient-centered care, which is more likely to result in the adhesion to the treatment plan and, thus, improved patient satisfaction (58, 59).

Regular testing of biomarkers may be beneficial for patients who are at risk for deficiencies or pathogenicity. Constant monitoring allows risk stratification of patients into low to high categories, considering both modifiable and nonmodifiable risk factors, as well as immune-metabolic indicated by biomarkers. The oral phenotype, determined by genetic, environmental, and microbial factors, is reflected by tissue integrity and immune functions that control the pathogenicity of the oral biofilms. Integrating gene biomarkers with conventional risk factors in a personalized medicine approach enables population stratification, aiding in resource allocation for preventive dentistry (60).

Apart from the rapid diagnosis, novel approaches allow for the implementation of various tests over an extended period to monitor progress or assess healing parameters, thereby preventing complications or relapse (Figure 2). When supplementation is needed, the periodic monitoring of biomarker levels is crucial to follow any fluctuation in serum concentrations. Thus, these novel testing methodologies offer a more advanced approach via the point-of-care testing and the optimization of the whole process. Therefore, mapping the levels before and after e.g., a surgical intervention is easier and with minimized outlay. Likewise, the importance of regular preventative visits is highlighted in literature. Giannobile et al. investigated insurance claims for 16 years for 5,117 adults retrospectively for tooth extraction events and reported significantly reduced tooth loss rates associated with increased preventive visits (60). Hence, emphasizing the importance of patient awareness, enhanced regular check-ups, as well as integration of marker screening and nutritional monitoring in patients’ treatment approaches to support improved clinical outcomes.

The development of new point-of-care technologies has revolutionized the way clinicians can test marker levels directly in their offices, eliminating the need for external laboratories involvement. This advancement not only allows for rapid diagnostics but also facilitates the formulation of personalized treatment plan (Figure 3). Furthermore, reducing chair time in dental offices improves efficiency and productivity for staff while potentially enhancing the overall patient's dental experience, as patients commonly associate dental procedures with discomfort. By minimizing chair time, patients are spared the inconvenience of scheduling additional appointments at external laboratories and then returning to the dental office for further consultations. Additionally, shorter chair time may contribute to more efficient scheduling and better outcomes. Instead, it can guide and triage the patient to any follow up or consultation in medical practice that are necessary post-screening. This interdisciplinary workflow, starting in the dental office, promotes pre-appointment preparation and excludes any additional testing reducing likelihood of missed cancer screening or skipped appointments for patients with limited time available. Ultimately, reducing chair time encourages patients to prioritize their oral health and ensures that they receive the necessary care promptly.

Oral health is increasingly recognized as an integral part of general health, prompting the integration of dental care into primary healthcare services (Figure 3). This shift has put the spotlight on various risk factors such as lifestyle, systemic conditions, diet and smoking, which contribute to oral diseases. Integration strategies not only advocate to raise awareness about oral health but also seek to enhance individual's willingness to prioritize it. The integration of oral health into primary care has been implemented to reduce the burden of oral diseases within the communities and to promote health education and empowerment. For example, the Longwood Harvard Dental Center (HDC) has launched an innovative project known as the Nurse Practitioner-Dentist (NPD) model for Primary Care in a dental practice environment. Recognizing the pivotal role nurse practitioners play in providing comprehensive healthcare services to patients, such as physical examinations, annual wellness check- ups, and counseling on nutrition and tobacco cessation. The program's goal is to optimize the value of each patient encounter by improving outcomes and delivering more holistic care through the seamless integration of these services into the dental visit. Other strategies concentrate on building interdisciplinary networks, training non-dental care providers and implementing e-health technologies (61). The ultimate goal is to integrate oral health into overall health, acknowledging the relationship between oral and systemic well-being.