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Compendium
May 2022
Volume 43, Issue 5

Unlocking Links to Oral and Systemic Health — Through Saliva

L. Eric Pulver, DDS

Oral healthcare providers have an opportunity to help position-of all things-saliva at the forefront of wellness. Saliva, with its easily accessible, simplified, and cost-effective screening, can be used to provide early identification, prevention, and monitoring of disease and, in time, may allow for precision therapeutics. Saliva can be an important key in fostering collaboration between oral and systemic healthcare providers, leading to enhancements in delivery of care. Sharing saliva insights in a compliant, secure manner allows both dental and medical providers to implement preventive care measures more efficiently and patients to become more readily aware and accept treatment of conditions requiring intervention. This can be done in an objective, standardized manner, at times at home, potentially resulting in high-precision action being taken earlier, with lowered cost, improved outcomes, and enhanced health and wellness.

Salivary Diagnostics: The Next Frontier in Oral Health

The perception of saliva has come a long way. Thanks to science, innovation, and technology, the medical and dental communities are now beginning to understand the abundant secrets saliva holds within. Testing can now evaluate down to the strain level for organisms and even deeper into the cellular and genomic levels.

Saliva represents dentistry's stealth "super power," a vector for change, holding the force to unite oral and systemic health providers and leading to improved population health and well-being. It has been estimated that 111 million people visit a physician each year and do not have a dentist,1 while 27 million people visited the dentist and had no medical doctor.2 This speaks to an opportunity for collaborative change by dentists working together with physician colleagues and engaging these patients and making appropriate referrals. This can lead to significant benefits for all stakeholders, including patients, oral healthcare providers, physicians, industry leaders, and payors with hopes of improving general population wellness.

Saliva alone is not enough; other innovative point-of-service tools traditionally provided by physician colleges should be considered and utilized within oral healthcare and telehealth networks. These new concepts will require champions, ambassadors, and carefully created systems for education and implementation with the goal of using saliva and other point-of-care (POC) and remote POC testing to sample a patient's systemic health, promoting early identification and prevention where possible.

Rena N. D'Souza, Director of the National Institute of Dental and Craniofacial Research, and colleagues recently published an article in the New England Journal of Medicine which stated that oral and gut microbiomes, combined with other "omics" (eg, metabolomics, proteinomics, salivariomics, transcriptomics), will provide the basis for therapies such as probiotics and mouthrinses that can be used "to address disease-associated oral microbial ecosystems and biofilms and create healthier ones."3

These same innovations and technologies can also provide a path forward for transformational change within the dental profession. Providing patients insight into their systemic health is not a new idea, nor is the use of saliva as a diagnostic tool; but, unfortunately, this concept has yet to become part of dentists' everyday armamentarium of care. However, it represents great opportunity. Oral healthcare providers have successfully demonstrated the ability to adapt to and negotiate through change and reinvention. Consider the overcoming of viral and bacterial challenges (eg, hepatitis C, HIV, COVID, water line contaminants), the changeover to digitalization (eg, impressions, smile design, lab processing, electronic medical records, radiographs), and many other challenges. Who better to lead the way forward, redefining and repositioning dentists' role in healthcare?

Inventing the Future

Consider this futuristic scenario: A woman wakes up and begins her daily routine, rinsing with saline and quickly supplying a 1 mL saliva sample into a POC biosensor, and another 1 mL sample sent on a personalized schedule for deep lab testing, while awaiting her daily automated stool and urinalysis analytics. She grabs her custom ultraviolet (UV)-activated eclectic intelligent toothbrush (antibacterial, immunotherapy, whitening) and smart non-abrasive personalized precision gel or paste and begins to brush.Feedback of brushing quality and pressure begins to be collected. Gamification of her brushing is linked to instantaneous points being totaled on her interactive health room mirror. Her intraoral biometric Internet of Things (IOT) wearable device collects data, such as pH, electrolytes, glucose, and biologics, which is shared through her smartphone app, while the interactive health room mirror is busy collecting real-time biostatistics (eg, pulse oximetry, heart rate variability, respiration rate, body temperature, stress levels, etc) and reporting her sleep statistics from her multisensor ring. Her intraoral nightguard sensor is relaying bruxing patterns and forces to an app collecting and analyzing this data. Aligner therapy can be incorporated into much of this new technology. Images can be used to monitor orthodontic progress and identify concerns requiring intervention and in-person visits throughout care. Data is processed and compared to historical trends and averages. Biostatistics and noiseless algorithms instantly compare and analyze, providing real-time evaluation, insight, and practical applications for implementation/integration into her daily routine.4 Further in the future this analysis can be run through her digital twin (including digital duplicated DNA) to determine how it may influence her daily routine and health status.5 (See "Technology Resources" sidebar for website information on the technologies referenced in this paragraph.)

Although not all readily available today, this technology-and associated morning scenario-may one day become a reality and play a significant role within the metaverse. Such technology will be able to provide daily individualized precision recommendations for diet, medication, dosage adjustments, exercise, etc, to help optimize cellular health and well-being. If necessary, a virtual consultation could be scheduled that focuses on prevention and health maintenance. Some of these technologies exist today, while others are being developed and may be available sooner than people expect.

Finding Oral and Systemic Health Links

Saliva has been associated with caries, inflammation, bad breath, gut biome, systemic health, neurodegenerative disease, drug monitoring, heredity, infection (viral, bacterial, fungal), autoimmunity, hormones, and malignancy.6,7 Not all saliva is the same, and work has been done to determine what type of saliva should be tested and when testing should be done. Whole saliva and/or its serum constituents coming from the cervical clavicular fluid may influence findings.6 Saliva testing has been used in dentistry for quite some time, with the Forsyth Institute serving as a leading research and innovation center for oral health and an incubator for advanced salivary diagnostics and enhanced oral healthcare.

Saliva testing has developed and advanced, allowing for greater understanding of disease and the prevention process. New genetic testing such as shotgun metagenomics8 can dive deep into the strains of bacteria and identify entire genomes allowing for cell atlases to be created and shedding new light on phenotypic expression. S16, a more shallow testing, has broken down specific selective known pathways that have proven to be useful tools to guide therapy.9 Electric field-induced release (EFIR) and measurement techniques may hold potential for salivary diagnostics and precision medicine.10 In time, POC smartphone biosensors may become available.11 The advantages and challenges of these test types are beyond the scope of this article, but they represent great promise in dentistry's journey forward.12

The multifaceted intelligence held within one's saliva can help unlock links, associations, and causalities between oral and systemic health. Continued research will enable better understanding of the complex language of healthy inter- and intracellular interaction leading to early identification, prevention, and mechanisms to support a learning healthcare system, expand precision medicine, and improve population health and wellness. These changes will require clear vision, a roadmap, frictionless integration, and the support of and engagement from early adopters working together to create change.

About the Author

L. Eric Pulver, DDS
Chief Dental Officer, Denti.AI; Adjunct Faculty, Indiana University School of Dentistry, Indianapolis, Indiana; Advisor, Bristle Health; Private Practice in Oral and Maxillofacial Surgery, Highland, Indiana; former Director OMFS, University of Chicago Hospitals; Fellow, Royal College of Dentists of Canada

References

1. Primary Care Collaborative. Integrating Oral Health in Primary Care. PCC website. January 2021. Page 17. https://www.pcpcc.org/resource/innovations-oral-health-and-primary-care-integration-alignment-shared-principles. Accessed March 29, 2022.

2. Vujicic M, Israelson H, Antoon J, et al. A profession in transition. J Am Dent Assoc. 2014;145(2):118-121.

3. D'Souza RN, Collins FS, Murthy VH. Oral health for all - realizing the promise of science. N Engl J Med. 2022;386(9):809-811.

4. Kahneman D, Sibony O, Sunstein CR. Noise: A Flaw in Human Judgment. New York, NY: Hachette Book Group; 2021.

5. Björnsson B, Borrebaeck C, Elander N, et al; Swedish Digital Twin Consortium. Digital twins to personalize medicine. Genome Med. 2019;12(1):4.

6. Kaufman E, Lamster IB. The diagnostic applications of saliva - a review. Crit Rev Oral Biol Med. 2002;13(2):197-212.

7. Ar P, Gulati A, Mehta D, Sugandhan S. Diagnostic applications of saliva in dentistry. Int J Clin Pediatr Dent. 2009;2(3):7-13.

8. Quince C, Walker AW, Simpson JT, et al. Shotgun metagenomics, from sampling to analysis. Nat Biotechnol. 2017;35(9):833-844.

9. Janda JM, Abbott SL. 16S rRNA gene sequencing for bacterial identification in the diagnostic laboratory: pluses, perils, and pitfalls. J Clin Microbiol. 2007;45(9):2761-2764.

10. Wang A, Wang CP, Tu M, Wong DT. Oral biofluid biomarker research: current status and emerging frontiers. Diagnostics (Basel). 2016;6(4):45.

11. Khan RS, Khurshid Z, Yahya Ibrahim Asiri F. Advancing point-of-care (PoC) testing using human saliva as liquid biopsy. Diagnostics (Basel). 2017;7(3):39.

12. Durazzi F, Sala C, Castellani G, et al. Comparison between 16S rRNA and shotgun sequencing data for the taxonomic characterization of the gut microbiota. Sci Rep. 2021;11(1):3030.

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