The Mouth-Body Connection: Exploring the Link by Investigating Leading Causes of Mortality

Jamie Toop, DDS

June 2019 Course - Expires June 30th, 2022

Updates in Clinical Dentistry

Abstract

This article discusses the leading causes of mortality in America and their relationship to oral health. It then explains how certain conditions are specifically related to the oral cavity, including atherosclerosis, type 2 diabetes, Alzheimer’s disease, pancreatic cancer, oral cancer, lung cancer, erectile dysfunction, and preterm birth. The article goes on to describe the need to manage risk factors that may lead to these conditions. It also emphasizes the need to provide education to increase awareness of the link between oral and systemic health in the interest of preventing and treating potentially deadly conditions.

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The eight leading causes of mortality in America are heart disease and heart attacks, cancer, chronic lower respiratory diseases such as bronchitis, accidents, cerebrovascular disease and strokes, Alzheimer's disease, diabetes, and influenza and pneumonia.1 Except for accidental death, the leading causes of mortality in America can be linked to conditions in the mouth in the form of viruses, bacteria, and inflammation.2,3 Periodontal disease and endodontic pathosis and associated inflammation and bacteria can lead to a greater incidence of the chronic and potentially fatal conditions listed above. Periodontal disease is the most common chronic infection in the United States and is also the largest source of inflammation in the body.4 When inflammation occurs, it is not isolated but rather can have systemic effects through bacteria and other entities that can enter the bloodstream and travel through the arteries.5 After reaching the arteries, these entities can create a new location of inflammation in the endothelium, resulting in a weakening of tissue that is usually tough, elastic, and resilient. Furthermore, if a plaque deposit has previously formed in the location, inflammation can allow the plaque to puncture through the weakened endothelium, leading to coagulation and potentially resulting in a heart attack or stroke.5

Atherosclerosis

The best predictor of a heart attack or stroke is the presence of atherosclerosis, which is a crucial step in vascular disease.6 Common pathogens originating in the mouth and associated with periodontitis play a role in atherosclerosis.

Aggregatibacter actinomycetemcomitans is associated with aggressive and chronic periodontitis and directly affects inflammation in the arteries. When A. actinomycetemcomitans is present in the bloodstream, it has been reported that the lining of the arteries can have trouble healing and replacing itself, and apoptosis has been seen.7 When healthy, the arterial walls are not permeable to the components of blood, but when A. actinomycetemcomitans is present, leukocytes are able to adhere to and pass through the endothelium and initiate inflammation. Through this process, A. actinomycetemcomitans originating in the mouth is linked to arthritis, atherosclerosis, and Alzheimer's disease.7

Like A. actinomycetemcomitans, Porphyromonas gingivalis plays a role in systemic inflammation. It has been reported that P. gingivalis accelerates atherosclerosis by promoting the production of pro-inflammatory ligands and inhibiting the production of anti-inflammatory ligands.8 Also, when P. gingivalis is present, the blood concentration of low-density lipoproteins, or "bad" fatty acids, is markedly higher, leading to greater deposition of plaque in the endothelium.8 Because of these processes, patients with periodontal disease are 24% to 34% more likely to develop plaque in their coronary arteries that may progress to heart disease.9 Also, those with gum disease are at a 4.5 times greater risk for an ischemic stroke.3 This cause-and-effect relationship is becoming more widely recognized, and level A evidence has been documented in peer-reviewed literature that supports the fact that the inflammation and pathogens associated with periodontitis directly cause atherosclerosis.10

Because of scientific evidence that healthy gums help prevent heart attacks and strokes, the editors of The American Journal of Cardiology and the Journal of Periodontology issued a consensus statement recommending that physicians and dentists warn patients with moderate to severe gum disease of their potential cardiovascular danger: patients with gum disease should get a complete physical examination and blood pressure measurement annually; patients with gum disease should be checked for diabetes, high cholesterol, and a family history of early deaths from cardiovascular disease (CVD); and patients with gum disease and one or more other CVD risk factors, such as high blood pressure or high cholesterol, should be treated with lifestyle changes and, if necessary, medication.11

Prospective Studies

Faculty at the Indiana University School of Dentistry published findings that showed systemic responses to gingivitis through a 21-day prospective study of dental students.12 After evaluating and documenting the condition of the students' periodontium, they instructed the dental students to abstain from all types of oral hygiene. Over the course of 21 days, statistically significant levels of endotoxemia (gram-negative bacteria in the bloodstream) in response to gingivitis were documented. After the students started practicing traditional methods of oral hygiene again, the endotoxemia was resolved. Endotoxemia is a prime cause of atherosclerosis and can occur in response to periodontal inflammation.

Type 2 Diabetes

Although a cause-and-effect relationship between type 2 diabetes and periodontal disease has not been definitively determined, studies have reported findings of higher diabetic risk in those who have periodontal disease. One study specifically found that patients with gingivitis were 40% more likely to be diagnosed for type 2 diabetes, with the risk elevating in relation to the progression of periodontal disease.13 Those with periodontitis had a 50% risk of developing diabetes. The patients with periodontitis and multiple missing teeth had a 70% increased risk of developing diabetes after the onset of periodontitis.13 Although more research is needed, there appears to be a relation between the increased risk of developing diabetes and the onset of periodontal disease. It is widely recognized that there is a bidirectional relationship between diabetic control and periodontal disease.14

United Concordia Study

The insurance company United Concordia commissioned a study looking into how money could be saved when periodontitis was addressed.15 Approximately 1.7 million insurance claims were reviewed over the course of 5 years; members who were diagnosed with periodontal disease and treated were compared with those who were diagnosed with periodontal disease and did not move forward with treatment. The company found that the patients who completed scaling and root planing and continued to return for 3-month periodontal maintenance therapy had lower overall medical care costs and fewer hospitalizations. Patients who were at risk for stroke, who had been diagnosed for cerebrovascular disease, saved $5,600 in healthcare costs and had 20% fewer hospitalizations on average per year when they were treated for their periodontal disease. Patients who were at risk for heart attacks, who had been diagnosed with heart disease, saved $1,000 in healthcare costs and were hospitalized 30% less often. Patients with diabetes saved $2,800 on average per year in healthcare costs and were hospitalized 40% less often than their counterparts who did were not treated for periodontitis. Studies of claims from other major insurance carriers have shown similar findings.16-18

Alzheimer's Disease

Because periodontal disease is associated with systemic bacteria and inflammatory factors, patients with periodontal disease are 2.6 times more likely to develop Alzheimer's disease.19 Alzheimer's disease involves the accumulation of tau and amyloid proteins in the brain, and its cause has long been a mystery. Studies published recently have suggested that P. gingivalis can cross the blood-brain barrier, where it can invade the regions of the brain associated with Alzheimer's disease and cause amyloid proteins in mice.20 P. gingivalis has also been found in spinal fluid of people living with Alzheimer's, leading researchers to suggest a possible test to diagnose the condition.20 Conclusions have been made that although more research is needed, P. gingivalis could be a cause of Alzheimer's.20

Pancreatic Cancer

Pancreatic cancer, which is difficult to detect and is usually diagnosed in the untreatable late stages of the disease, is the fourth-leading cause of cancer-related deaths; the 5-year survival rate is just 8%.21 Oral gram-negative organisms have been associated with an acutely increased risk of pancreatic cancer. P. gingivalis and A. actinomycetemcomitans, which are linked to atherosclerosis and Alzheimer's, are also linked to elevated pancreatic cancer rates.22 San Diego State researchers found that patients with pancreatic cancer had high levels of two types of bacteria in their saliva: Campylobacter and Leptotrichia.23 The researchers were able to develop a salivary test measuring the presence of these two microorganisms that yields earlier predictions than any previous test, which can lead to early detection and treatment of pancreatic cancer. This screening method under development may be performed by dental care providers.23

Oral Cancer

When evaluating present literature, it appears that there is a link between oral/oropharyngeal cancers and periodontitis. Some studies have reported up to a 5-fold increased incidence of oral cancer when individuals have periodontal disease.24 Recession caused by periodontal disease has also been linked to greater oral and oropharyngeal cancers. Each millimeter of recession was associated with a 5-fold increased risk for these types of cancers after common confounding factors were considered.24 Total cancer risk also appears to increase in the body when periodontal disease is present. Specifically, it has been reported that total cancer risk is increased by as much as 14% in those who have periodontal disease.24

The periodontal-cancer connection appears to result through several different means. First, prostaglandins and cytokines, along with inflammation, are involved in both the cancer and periodontal disease processes.24 The periodontal disease process also involves tumor necrosis factor-alpha, which is found in early development of tumors that lead to cancer and is thought to seed tumor development.25 Lastly, deep periodontal pocketing harbors pathogens such as viruses and bacteria that are associated with greater likelihood of developing oral cancer and oropharyngeal cancer.24

After being diagnosed with oral cancer, just one of every two patients will continue to live another 5 years; these statistics have not shown much improvement in recent years.24 Early screening of every patient is crucial, which may include visual inspection, visual inspection under fluorescence, and salivary pathogen testing.

Lung Cancer

Periodontal pathogens can also be inhaled through aspiration and cause respiratory infections. In the case of pneumonia, aspiration of bacteria originating in the oral cavity can initiate a new location of irritation and infection in the lungs. A causal relationship has been documented where periodontal bacteria can cause lung irritations and infections.26 P. gingivalis, Fusobacterium, and A. actinomycetemcomitans have been documented as responsible; a gradient effect occurs in which more infection and loss of lung function are associated with higher loads of P. gingivalis, Fusobacterium, and A. actinomycetemcomitans.26,27

Erectile Dysfunction and Preterm Birth

Periodontal disease affects men and women in uniquely different ways. Like the atherosclerosis etiology discussed earlier, impotence and erectile dysfunction in men can be a result of micro-damage of vasculature caused by inflammation.28 Higher rates of preterm birth occur among women with micro-damage to vasculature caused by inflammation in the umbilical cord, which can lead to decreased perfusion of nutrients to the developing fetus.29 Another theory is that placental membranes may prematurely rupture in the presence of inflammation. In a study that evaluated placentas of babies born preterm, P. gingivalis was found in most cases. Although more research is needed, some research has found that mothers with gingivitis had a 3 times higher rate of giving birth preterm and that those with moderate periodontitis had an 8 times higher rate of giving birth preterm or to a baby with low birth weight and in need of additional care in the neonatal intensive care unit.29

Periapical Periodontitis

Although meta-studies have not yet demonstrated a clearly defined connection, endodontic pathosis has been suggested as a source for potential systemic maladies. Several studies have shown a connection between failing root canals and heart disease.30-32 However, further research is needed to establish a causal relationship. Reasons why a causal relationship has not yet been found include lack of control groups and lack of uniform parameters, which make many results difficult to compare.

Potential Solutions

Further research is needed to fully investigate the nature of oral-systemic links, but a trend has emerged suggesting systemic decline occurs when periodontal disease and endodontic pathogens are left untreated. Periodontal disease and endodontic abscesses should be treated thoroughly and with whole-body wellness in mind. It is important to discuss what the dental community can and should do to accomplish these goals.

The dental community must increase wellness by diagnosing periodontal disease and periapical pathosis and treating it effectively. Dentists can implement follow-up testing after treatment is completed to assure these infections are eliminated or well controlled. It is also critical to focus on patient education, educating the medical community when needed, and using screening methods for detecting disease and determining whether the disease is controlled.

Gingivitis Treatment

Inflammation associated with gingivitis can cause systemic effects. Bacteria and toxins can enter the bloodstream in healthy young adults with gingivitis.12 Pregnant mothers with gingivitis have a 3 times higher risk of giving birth preterm.29 Patients with gingivitis have a 40% elevated risk of developing type 2 diabetes.13 Although more research is needed, early studies of P. gingivalis associated with gingivitis show links to Alzheimer's; it may affect regions in the brain that cause cognitive decline presenting 10 to 20 years later.20 Knowing this, oral healthcare providers may want to approach therapy for gingivitis differently. Instead of treating the condition with a simple prophylaxis every 6 months while watching for signs of periodontitis, gingivitis can be treated early and effectively, including a system of follow-up visits to ensure inflammation is well controlled.

A similar strategy can be considered for periodontitis. The harmful and lasting effects that can be seen in the body due to a periodontal infection have been well-documented.2 It is critical to treat periodontal disease and schedule postoperative visits to ensure the disease is well controlled. If follow-up visits continue to show disease that is not well controlled, dentists can also use salivary bacterial testing and partner with the patient's physician.

Salivary Diagnostics

Salivary testing is a helpful tool that dentists can implement as a precursor and follow-up to periodontal treatment. Completing the test before periodontal therapy can establish a baseline; completing the test again after treatment will determine whether treatment was successful. Additional salivary testing during a follow-up visit after treatment can help ensure the bacterial load has responded to therapy and is no longer a threat to the patient's overall health.

Patient Education

It is important to educate patients on the links between the mouth and body and help them understand how they can potentially be healthier with the recommended treatment. Providing such education is also a means for dentists to differentiate their practice. An altruistic approach to care can give the patient a strong reason to remain loyal to the practice and refer friends and family.

Three steps that are useful in educating patients about whole-body wellness: 1) At a patient's first visit, a dentist can personally sit down with the patient and ask about individual and family history of systemic conditions that can be linked to the mouth. 2) The dentist can inform the patient that if certain conditions present that have been known to worsen or lead to a higher incidence of systemic conditions, the dentist will highly recommend that those conditions be treated quickly and effectively, including a follow-up examination to ensure the treatment was successful. 3) The dentist can convey a desire to partner with the patient's physician to keep the patient as healthy as possible.

Educating the Physician, Physician Assistant, and Other Medical Providers

For each patient diagnosed with periodontal disease, a dentist can send a letter to that patient's physician outlining the patient's condition, the proposed dental treatment, the systemic affiliations of that condition, and a request that the physician screen and monitor for affiliated conditions.

Dentists can also work closely with and educate other medical providers in their community. It may be helpful for dentists to make an introduction to local medical providers and offer them literature from medical journals supporting the mouth-body connection. Obstetrician-gynecologists, cardiologists, internists, and family care physicians all have patients who are affected by P. gingivalis and A. actinomycetemcomitans. Many medical doctors are aware of the link between the mouth and body and know how their patients can be negatively affected by an unresolved oral health condition. Dentists can offer their practice for patient referrals.

Conclusion

Oral healthcare providers save lives by providing quality, comprehensive dentistry. Current research shows that seven of the eight leading causes of mortality are linked to conditions in the mouth such as periodontal disease and potentially endodontic pathology. Oral pathogens and inflammatory mediators link oral disease to multiple systemic conditions; therefore, it is important to treat periodontal disease and endodontic abscesses with whole-body wellness in mind.

About the Author

Jamie Toop, DDS, graduated from Loma Linda University School of Dentistry and is an owner-dentist in Las Vegas, Nevada, supported by Pacific Dental Services (PDS). Dr. Toop is a recognized expert in the mouth-body connection.

References

1. Leading causes of death. Centers for Disease Control and Prevention. https://www.cdc.gov/nchs/fastats/leading-causes-of-death.htm. Accessed February 28, 2019.

2. Winning L, Linden GJ. Periodontitis and systemic disease. BDJ Team. https://www.nature.com/articles/bdjteam2015163. Published November 27, 2015. Accessed February 28, 2019.

3. Grau AJ, Becher H, Ziegler CM, et al. Periodontal disease as a risk factor for ischemic stroke. Stroke. 2004;35(2):496-501.

4. Loesche WJ, Grossman NS. Periodontal disease as a specific, albeit chronic, infection: diagnosis and treatment. Clin Microbiol Rev. 2001;14(4):727-752.

5. Gurenlian JR. Inflammation: the relationship between oral health and systemic disease. American Dental Hygienists' Association. https://www.adha.org/sites/default/files/7823_Inflammation.pdf. Published April 2006. Accessed February 28, 2019.

6. Atherosclerosis. National Heart, Lung, and Blood Institute. https://www.nhlbi.nih.gov/health-topics/atherosclerosis. Accessed April 4, 2019.

7. Dietmann A, Millonig A, Combes V, et al. Effects of Aggregatibacter actinomycetemcomitans leukotoxin on endothelial cells. Microb Pathog. 2013;61-62(100):43-50.

8. Rufail ML, Schenkein HA, Barbour SE, et al. Altered lipoprotein subclass distribution and PAF-AH activity in subjects with generalized aggressive periodontitis. J Lipid Res. 2005;46(12):2752-2760.

9. Humphrey LL, Fu R, Buckley DI, et al. Periodontal disease and coronary heart disease incidence: a systematic review and meta-analysis. J Gen Intern Med. 2008;23(12):2079-2086.

10. Bale BF, Doneen AL, Vigerust DJ. High-risk periodontal pathogens contribute to the pathogenesis of atherosclerosis. Postgrad Med J. 2017;93(1098):215-220.

11. Friedewald VE, Kornman KS, Beck JD, et al. The American Journal of Cardiology and Journal of Periodontology editors' consensus: periodontitis and atherosclerotic cardiovascular disease. J Periodontol. 2009;80(7):1021-1032.

12. Wahaidi VY, Kowolik MJ, Eckert GJ, Galli DM. Endotoxemia and the host systemic response during experimental gingivitis. J Clin Periodontol. 2011;38(5):412-417.

13. Borgnakke W, Ylöstalo PV, Taylor GW, Genco RJ. Effect of periodontal disease on diabetes: systematic review of epidemiologic observational evidence. J Periodontol. 2013;84(4 suppl):S135-S152.

14. Chee B, Park B, Bartold PM. Periodontitis and type II diabetes: a two‐way relationship. Int J Evid Based Healthc. 2013;11(4):317-329.

15. The mouth: the missing piece to overall wellness and lower medical costs. United Concordia. https://www.unitedconcordia.com/docs/united%20concordia%20oral%20health%20whitepaper.pdf. Published 2014. Accessed February 28, 2019.

16. Improved health and lower medical costs. Cigna Health and Life Insurance Company. https://www.cigna.com/static/www-cigna-com/docs/employers-brokers/dental-white-paper.pdf. Published June 2016. Accessed February 28, 2019.

17. Nasseh K, Vujicic M, Glick M. The relationship between periodontal interventions and healthcare costs and utilization. Evidence from an integrated dental, medical, and pharmacy commercial claims database. Health Econ. 2017;26(4):519-527.

18. Edlin M. Good oral care evolves into new preventive disease tool. Managed Care Executive. https://www.managedhealthcareexecutive.com/benefit-design-and-pricing/good-oral-care-evolves-new-preventive-disease-tool. Published March 1, 2008. Accessed February 28, 2019.

19. Kondo K, Niino M, Shido K. A case-control of Alzheimer's disease in Japan-significance of life-styles. Dementia.1994;5(6):314-326.

20. MacKenzie D. We may finally know what causes Alzheimer's - and how to stop it. New Scientisthttps://www.newscientist.com/article/2191814-we-may-finally-know-what-causes-alzheimers-and-how-to-stop-it/. Published January 23, 2019. Updated January 30, 2019. Accessed February 28, 2019.

21. Pancreatic cancer facts 2016. Pancreatic Cancer Action Network. https://www.pancan.org/wp-content/uploads/2016/02/2016-GAA-PC-Facts.pdf. Published February 2016. Accessed February 28, 2019.

22. McGinley L. These oral bacteria are linked to an increased chance of getting pancreatic cancer. The Washington Post. https://www.washingtonpost.com/news/to-your-health/wp/2016/04/20/these-oral-bacteria-might-increase-your-chances-of-getting-pancreatic-cancer/?utm_term=.4fce2cf49c75. Published April 20, 2016. Accessed February 28, 2019.

23. American Society for Microbiology. Bacteria in mouth may diagnose pancreatic cancer. Science Daily. https://www.sciencedaily.com/releases/2014/05/140518164419.htm. Published May 18, 2014. Accessed February 28, 2019.

24. Lamster I, Collins F. Periodontitis and oral cancer. Colgate Oral Health Network. https://www.colgateoralhealthnetwork.com/article/periodontitis-and-oral-cancer/. Accessed February 28, 2019.

25. Wang X, Lin Y. Tumor necrosis factor and cancer, buddies or foes? Acta Pharmacol Sin. 2008;29(11):1275-1288.

26. Linden GJ, Herzberg MC; Working group 4 of joint EFP/AAP workshop. Periodontitis and systemic diseases: a record of discussions of working group 4 of the Joint EFP/AAP Workshop on Periodontitis and Systemic Diseases. J Clin Periodontol. 2013;40(suppl 14):S20-S23.

27. Geppert EF. Chronic and recurrent pneumonia. Semin Respir Infect. 1992;7(4):282-288.

28. Singh VP, Nettemu SK, Nettem S, et al. Oral health and erectile dysfunction. J Hum Reprod Sci. 2017;10(3):162-166.

29. Saini R, Saini S, Saini SR. Periodontitis: a risk for delivery of premature labor and low-birth-weight infants. J Nat Sci Biol Med. 2010;1(1):40-42.

30. Haraszthy VI, Zambon JJ, Trevisan M, et al. Identification of periodontal pathogens in atheromatous plaques. J Periodontol. 2000;71(10):1554-1560.

31. Mattila KJ, Pussinen PJ, Paju S. Dental infections and cardiovascular diseases: a review. J Periodontol. 2005;76(11 suppl):2085-2088.

32. Mahendra J, Mahendra L, Kurian VM, et al. 16S rRNA-based detection of oral pathogens in coronary atherosclerotic plaque. Indian J Dent Res. 2010;21(2):248-252.

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PROVIDER: Dental Learning Systems, LLC
SOURCE: Updates in Clinical Dentistry | June 2019
COMMERCIAL SUPPORTER: PDS University—Institute of Dentistry

Learning Objectives:

  • Identify statistics from current research on the link between diseases of the mouth and body.
  • Identify potential mechanisms that link diseases of the mouth and body.
  • Identify the implications of research as it relates to the patient and the medical and dental communities.

Disclosures:

Dr. Toop currently serves as a faculty member of the PDS University—Institute of Dentistry and a member of the PDS National Advisory Board.

Queries for the author may be directed to jromano@aegiscomm.com.