Oral Infection—Systemic Disease Connection

White Paper Report
Oral Infection—Systemic Disease Connection
William D. Nordquist DMD MS, William C Domb DMD, William Landers, Chris Kammer DDS, Lisa Marie Samaha DDS, Chelsea Elliot Martin DDS
Oral Microbes and Systemic Disease

Over the last twenty plus years, dental disease has been reported to be associated with numerous systemic diseases1, including, heart disease2 3 4 5 6 7 8 9, atherosclerotic lesions10 11, diabetes12 13, and neurological diseases14 15 16 17 18 19 20 21 22 23, brain abscesses24, precancerous gastric lesions25, prostate cancer26, and other cancers27 28 29. Although there have been numerous theories as to why this relationship exists, causation remains elusive30.

In this paper, we will attempt to describe the dilemma dentistry is facing when trying to mitigate the problems derived from new evidence that contradicts our basic understanding of dental disease as related to systemic disease. Thus, this new understanding requires that our professional methods moves beyond traditional approaches in the diagnosis and treatment of dental infection.
As-yet-uncultivated Oral Phylotypes

As-yet-uncultivated oral phylotypes have been detected in blood samples in episodes of bacteremia following dental procedures31, ventilator-associated pneumonia32, sinusitis33, sputa from cystic fibrosis patients34, and intrauterine infection leading to preterm birth or spontaneous abortion35. Nordquist and Krutchkoff36, as well as others37, propose evidence that a gross overpopulation of one or many spirochetal species plays an important role in periodontal disease. This finding is based on observation of chronic systemic disease symptoms that are reminiscent of other spirochetal diseases including Lyme disease, relapsing fever, and syphilis.

Traditional culturing techniques of identification of oral microbes in systemic diseases has proved impossible. However, advancements in DNA sequencing (and 16S RNA) analysis have proved invaluable. Siqueira and Rôças, reported 40-60% of the bacteria found in both healthy and diseased oral sites remain to be grown in vitro, phenotypically characterized, and formally named as species38. Therefore, the total number of different oral bacteria species has doubled from about 600 to as many as 1,200.

Like caries and periodontal diseases, the breadth of bacterial diversity in endodontic infections has been substantially expanded by culture-independent molecular methods.39 Sakamoto et al40 reported that uncultivated phylotypes accounted for approximately 55% of the taxa found in root canals of teeth with apical periodontitis. In pus aspirates from acute apical abscesses, as-yet uncultivated phylotypes encompassed approximately 24-46% of the taxa found41 42. Rôças43 reports, the “red complex” (Bacteroides forsythus, Porphyromonas gingivalis, and Treponema denticola) known for their pathology in periodontal disease is also a contributor to apical infection in necrotic teeth. Another demonstrated that the microbiota of symptomatic periapical lesions is predominated by anaerobic bacteria but also contains substantial levels of

Streptococci, Actinomyces, and genera not previously identified in the oral cavity44.
Traditional culturing techniques are useless when evaluating possible pathogenic microbes in periodontal disease. Alternative methods need to be developed until most oral microbes can be identified and characterized. This will take years and potentially significant fiscal expense to accomplish. Therefore, traditional techniques using phase contrast or dark field microscopy technology may be an alternative interim method to bridge the gap in DNA analysis knowledge. There are, of course, services that use DNA data to provide information on imputed levels of specific ‘pathogens’. While valuable, these markers are nowhere near as reliable as we might like to recognize ongoing disease processes or predict with great reliability the likelihood of further breakdown or disease control.

Seek Out and Find Dental Infection
The traditional method for diagnosing periodontal disease comprises using a mechanical periodontal probe with millimeter marks. This probe measures dental pockets around the teeth. When bleeding points occur, these are counted. The two measurements are then used for diagnosis. Considering the gravity of the relationship between dental disease and systemic disease, this method of mechanical diagnosis without evaluating the specific bacteria seems antiquated. Since periodontal disease is an infection, it is paramount to observe the microbes causing the infection directly facilitating identification of specific groups of bacteria, their relative populace related to each other, and their mode and rapidity of movement.
We also need to recognize that the damage seen in periodontal disease is not simply from direct action of the microorganisms against host structures. It may well be the host’s REACTION to these microbes that results in the destruction of host structures. It is the host who generates the matrix metalloproteinases that destroy the integral collagen.45 Host levels of inflammatory response must also be modulated to minimize further structural degradation.

When diagnosing necrotic teeth, the traditional periapical x-ray leaves much to be desired. In the early 2000’s, new Cone Beam Computed Tomography (CBCT) technology has revolutionized dentistry by its ability to diagnosis minute bone lesions in 3-D high definition.
Dental Diagnostic Tools

Diagnosis of periodontal disease: The periodontal microbe milieu can be evaluated using the phase contrast microscope electronically enhanced to 5,000X. The microscope is used to calculate imbalances of oral bacteria–specifically oral spirochetes–located in dental plaque. Observation of spirochetal overpopulation signifies a gross imbalance in oral microbes that is easy to recognize. Once detected, diagnosis and treatment options can be formulated. Since there are approximately 60 strains of oral spirochetes, most of which are, as-yet, uncultivated, the microscope is the only available method of identification. Many spirochetes are so minuscule, that they are not visible below the electronic boost to 5,000X. In most cases of severe periodontal disease, oral spirochetes, an easily identifiable microbe, can represent most of the visible oral bacteria by number.46

Diagnosis of infection located at the apex of necrotic teeth and failed root canal treated teeth: CBCT technology is capable of very high definition, offering as many as 1000 slices. A CBCT image can diagnose periapical lesions associated with abscessed teeth, including those lesions located below the root tips of teeth that have been successfully treated. With the advent of this new technology, it has been embarrassingly evident that many lesions are not visible using traditional digital dental radiology. Research has shown that all x-ray-detectable lesions associated with root canal treated teeth have an active inflammatory infiltrate47 48 49 and thus an area source of microbes capable of seeding other parts of the body. Moreover, even if these lesions could be diminished via nonsurgical treatment, such lesions may well spread inflammatory cytokines and other necrotic waste products throughout the system with further inflammatory or pathogenic effects. Plus, these oxygen starved nooks within the bone would serve as rich reservoirs for re-colonization of anaerobic microbes.
Treatment Options
Periodontal disease: Treating periodontal disease requires diagnosis, elimination of pathogenic species, and repopulation of the crevicular microbiome. Research has shown that many oral pathogens enter and incubate within gingival sulcus epithelial cells50. Therefore, one efficacious method to eliminate these intracellular bacteria along with gingival sulcular microbes is vaporizing them with a micro-beam CO2 laser. Others have employed electrosurgery to achieve desired therapeutic results. Ozone in a variety of forms has also been employed with primary reported anecdotal evidence of success. Then oral hygiene methods both in-office and at home should be used to minimize reinfection. The problem remaining after sterilizing the diseased gingival sulcus is rebalancing the microbes. Since recent DNA sequencing analysis has shown twice as many bacteria associated with periodontal and tooth periapical disease than previously reported with traditional culturing techniques, the search for the critical balance of normal flora is the forefront of research today51.
Endodontic lesions: When extensive decay results in the death of a tooth with a resulting necrotic pulp, endodontic treatment is traditionally performed by dentists. Endodontic treatment is employed to remove and decontaminate the central infected portion of the nerve chamber and main canals of the tooth. However, it is well known by dentists that Root Canal Therapy (RCT) does not effectively remove all the infection associated with the necrotic tooth. Thousands of dentinal tubules exist within the tooth dentin, each containing a pain sensitive mechanism that innervates the interior of a tooth. Once the tooth dies, these tubules serve as nutrient rich nooks for colonization of bacteria and collect necrotic products that most likely cannot be removed by traditional endodontics.
Additionally, the bacteria from the infected canals inevitably escapes through the periapical openings and into the surrounding bone. Said bacteria are then able to access the microvasculature that supplies the bone and migrate throughout the cardiovascular system52.
It might therefore, be concluded that extraction is the most predictable, reliable and effective method of treating necrotic teeth. Furthermore, it stands to reason that previously completed endodontic treatment should be evaluated at frequent intervals for radiolucent apical lesions or other signs of infection and inflammation, preferably including CBCT scans. Any evidence of bone loss at the apex predicts infection remaining associated with the tooth. Therefore, to give the patient the best chance for eliminating oral and systemic infection, necrotic teeth with apical lesions must be sacrificed for the better health of the body in general. Aggressive curettage of the bony socket, decontaminating the surrounding area, application of the CO2 laser and bone grafting is advisable to allow healing with a lowered risk of pathologic infection. If the patient insists on saving the tooth, thorough and aggressive endodontic therapy incorporating ozone will be necessary. If an apical lesion exists, then a surgical procedure is called for to eliminate the lesion followed by rigorous curettage, decontamination with the laser, and grafting. It is highly advisable to give the patient verbal and written informed consent to verify understanding that some of the infection may not be completely removed and can cause local or systemic problems in the future.
The dental professional’s paradox or the decision matrix one must employ when making treatment decisions for patients is daunting. It is not 100% certain there is a causal relationship between periodontal/endodontic infection and systemic sequalae, but mountains of credible evidence have been collected over many years to convince even the most skeptical critic. For many, this is not enough to change years of what is considered the Standard of Care treatment for dental disease.
As suggested by the nine principles of the Bradford Hill criteria, once the probability of a causal relationship is established prompt action is needed. Given the strength of the evidence, should one not make every effort to treat the disease states? Our collective professional sense is that the downsides are minuscule by comparison to the potentially devastating effects chronic infection and inflammation can have on the entire organism in comparison to the comorbidities of performing the dental treatments.
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