Endodontic Endotoxemia: The Oral-Systemic Connection

Did you know that one in three Americans has untreated tooth decay?¹ One in two has a history of gingivitis?

Its worst manifestation, periodontal disease, affects nearly 50% of people over the age of 30 in the United States.²

Even as I routinely inquire about oral hygiene with my patients, these numbers are … astonishing to me.

Are we doing enough?

The link between oral health and systemic health is undeniable. The most common oral diseases that plague humankind are cavities and periodontal disease, both of which are caused by oral dysbiosis.

Periodontal disease, which is oral dysbiosis accompanied by a hyperactive immune response and tissue destruction, increases the risk for cardiovascular disease,³ rheumatoid arthritis,⁴ diabetes,⁵ cancers,⁶ and inflammatory bowel disease.⁷ Diabetics are three times more likely to develop periodontal disease than their non-diabetic counterparts.^5,6 Pathogens from the mouth have been found in atherosclerotic plaques ⁸ in the brains of Alzheimer’s patients and in the joints of rheumatoid arthritis patients,⁹ and simple interventions such as brushing and flossing can reduce new cardiovascular events in patients with coronary artery disease³ and lower inflammatory markers such as C-reactive protein (CRP).*¹⁰

Aside from cardiovascular disease, Alzheimer’s, rheumatoid arthritis, diabetes, and IBD, dysbiosis and inflammation in the mouth increases the risks of cancers.

Periodontal disease increases the chances of developing:

• Gastric cancer
• Pancreatic cancer
• Head and neck cancer (four-fold)
• Tongue cancer (five-fold)

In people who do not brush their teeth, the risk of esophageal cancer is doubled. On the other hand, good dental hygiene practices can reduce a person’s risk of oral cancers by 62%.⁶

Mechanisms Explaining the Oral-Systemic Link

It all seems pretty mind-boggling. So, how is this happening? Of course, we’re only now beginning to flesh out mechanisms and much remains unknown, but there are some good ideas.

First, the microbes

Let’s not forget that there is approximately a 45% overlap in the microbes that inhabit the mouth and the gut!¹¹ Every day, we’re swallowing one trillion oral microbes into the gastrointestinal tract.¹¹ This means that the mouth has a direct effect in real time on the downstream organs, including the esophagus, stomach, and intestinal tract. If the mouth is inflamed and gums are bleeding and sore, then you are swallowing inflammatory cytokines into the gut (just think about this constant wash over the GI tract of INF-gamma, IL-6, TNF-alpha, white blood cells, etc … ).

Bacteremia, endotoxemia and inflammation

While swallowing pathogens, endotoxin or cytokines may be one-way inflammation and disease spread from the oral cavity to the GI tract, bacteremia may be another route for the mouth to influence the cardiovascular system, joints, and metabolism. The oral mucosa (or the epithelial lining of the mouth) is actually more porous than the gastrointestinal mucosa.¹² Unlike the gut, teeth extend through the oral mucosa, leaving a vulnerable point of entry in the protective epithelial barrier of the mouth. On a routine basis, bacteria rush into the bloodstream with each brushing, meal, or dental cleaning. Oral bacteria have also been found in the blood following dental procedures.⁸

One hypothesis for the oral-systemic link is that the mouth of someone with periodontal disease represents a large, inflamed surface area that is rich in dysbiotic microbes. Frequent, transient bacteremia exposes the system to chronic, low-grade inflammation.⁶¹ Basically, dysbiotic oral microbes and inflammatory cytokines are flooding the bloodstream all day, every day.

Leaky mouth

Drawing on our lessons from Functional Medicine about leaky gut, the epithelial barrier in the mouth could be damaged and leaking, resulting in, “leaky mouth.” It is a natural extension of the concept of intestinal permeability (“leaky gut”), whereby epithelial cells of the gastrointestinal tract are damaged, permitting harmful proteins and organisms into the bloodstream. The mucosa of the mouth is very porous, even in a healthy person, but low-grade inflammation and infection in the mouth could further damage the barrier between the oral mucosa and the bloodstream. This could trigger permeability, immune dysfunction, inflammation, and ultimately, systemic disease.¹³

What does this mean for clinical practice?

We must consider the oral cavity when we assess the health of the whole person. The oral cavity is positioned at the front entrance to the gastrointestinal tract and is therefore a vital component in restoring health to the gut. The oral cavity is nearly identical in layout and architecture to the gut. We can use our go-to gut treatments to support health in the oral cavity, which is imminently accessible. We can modulate the oral microbiome with chewable probiotics like Streptococcus salivarious, probiotic toothpaste, or antimicrobial oral sprays/solutions. We can calm inflammation and promote tissue healing with aloe vera juice, glutamine, zinc carnosine, and more. [I often prescribe a simple glutamine “swish and spit” for stomatitis. Easy, effective.]

Brushing, flossing, cleaning the tongue, and regular dental check-ups are important to control dysbiosis in the mouth, the gut, and to reduce the risk of heart disease, metabolic syndrome, and inflammatory joint pain. It’s essential for us to collaborate with our dental colleagues when patients have elevated CRP or chronic disease in the oral cavity because undoubtedly it is contributing to disturbances elsewhere in the system. The mouth is a key player in systemic health and we should embrace it as part of a comprehensive healing protocol.

References

1. Prodegin: lactobacillus support for oral health and weight management. Reno, NV: Klaire Labs, a division of ProThera;2011.
2. Bingham CO, 3rd, Moni M. Periodontal disease and rheumatoid arthritis: the evidence accumulates for complex pathobiologic interactions. Current opinion in rheumatology. 2013;25(3):345-353.
3. Reichert S, Schlitt A, Beschow V, et al. Use of floss/interdental brushes is associated with lower risk for new cardiovascular events among patients with coronary heart disease. Journal of periodontal research. 2015;50(2):180-188.
4. Araujo VM, Melo IM, Lima V. Relationship between Periodontitis and Rheumatoid Arthritis: Review of the Literature. Mediators of inflammation. 2015;2015:259074.
5. Bascones-Martinez A, Matesanz-Perez P, Escribano-Bermejo M, Gonzalez-Moles MA, Bascones-Ilundain J, Meurman JH. Periodontal disease and diabetes-Review of the Literature. Medicina oral, patologia oral y cirugia bucal. 2011;16(6):e722-729.
6. Meurman JH. Oral microbiota and cancer. Journal of oral microbiology. 2010;2.
7. Brito F, Zaltman C, Carvalho AT, et al. Subgingival microflora in inflammatory bowel disease patients with untreated periodontitis. European journal of gastroenterology & hepatology. 2012.
8. He J, Li Y, Cao Y, Xue J, Zhou X. The oral microbiome diversity and its relation to human diseases. Folia microbiologica. 2015;60(1):69-80.
9. Ogrendik M. Rheumatoid arthritis is an autoimmune disease caused by periodontal pathogens. Int J Gen Med. 2013;6:383-386.
10. Frisbee SJ, Chambers CB, Frisbee JC, Goodwill AG, Crout RJ. Association between dental hygiene, cardiovascular disease risk factors and systemic inflammation in rural adults. Journal of dental hygiene : JDH / American Dental Hygienists’ Association. 2010;84(4):177-184.
11. Segata N, Haake SK, Mannon P, et al. Composition of the adult digestive tract bacterial microbiome based on seven mouth surfaces, tonsils, throat and stool samples. Genome Biol. 2012;13(6):R42.
12. Devine DA, Marsh PD, Meade J. Modulation of host responses by oral commensal bacteria. Journal of oral microbiology. 2015;7:26941.
13. Nelson-Dooley C, Burhenne M. The Mouth-Body Connection: Why We Shouldn’t Ignore the Oral Microbiome. Mouth-Body Connection 2015; http://askthedentist.com/oral-microbiome/. Accessed Dec 22, 2015.