Systemic Diseases and the Oral Microbiome
The Mouth's Influence on the Heart, Lungs, and Everything Else

Long before we knew about the oral microbiome, or even the existence of microbes, the ancient Greek doctor Hippocrates was said to cure systemic diseases by pulling infected teeth (1). Sound crazy to you? Indeed, it sounds crazy to a lot of other people, including modern-day dental and medical professionals. Even if we’ve heard of this theory, many of us are still trying to wrap our minds around it. In truth, how can the mouth be the cause of some systemic diseases? So, let’s see how systemic diseases may relate to dysbiosis in the oral microbiome.

A brief review of the oral microbiome

The mouth hosts one of the most significant microbiomes because it is the gateway to the rest of the body. Firstly, it is where the immune system meets the outside environment: food, microbes, and pathogens. Importantly, the mouth is the gateway to the gut. This matters because the gut microbiome is the biggest and best studied of our microbiomes. Nonetheless, maintaining balance between “good” symbiotic bacteria and “bad” pathogenic bacteria is a key to maintaining overall health. For more, see our post on oral microbiome basics for autoimmune patients. For a deeper dive, see our oral microbiome e-book.

How can the oral microbiome cause systemic diseases?

New understanding of the oral microbiome is shaping how we think about caries, periodontal disease, and systemic diseases. The traditional view held that these diseases were caused by a few nasty pathogens. However, we now think of the oral microbiome as a finely tuned ecosystem. Nevertheless, an imbalanced microbe community not only causes oral disease, but also some systemic diseases (2).

Three pathways from the oral microbiome to systemic disease

1. Metastatic Infection. Bacteria from oral infections or released by dental procedures get into the blood and circulate through the body. Subsequently, these disseminated microorganisms may find favorable conditions. If they settle at a given site, over time they may multiply, colonize and trigger an immune response.
2. Metastatic Injury. Certain bacteria produce toxins that, when excreted or introduced into a host body, can trigger many pathological responses.
3. Metastatic Inflammation. Soluble molecules that enter the bloodstream may react with circulating antibodies. Then, these reactions produce large complexes that give rise to acute and chronic inflammatory reactions. (3)

Let’s examine this in the light of the second most common oral disease in the world: periodontal disease. Let’s see how periodontitis is connected to cardiovascular disease, diabetes, and cancer.

Now allow me to introduce (drumroll please)

Periodontal disease!

Periodontal disease refers to inflammatory processes in the tissues surrounding the teeth. For example, such processes are immune reactions to bacterial accumulations, or dental plaque, on the teeth (4). Furthermore, anaerobic bacteria from invasive microbial plaque can penetrate gingival (gum) tissues. Consequently, they can destroy tissue and trigger inflammatory responses. Inflammation involves white blood cells (leukocytes) such as lymphocytes and macrophages. Not to mention more leukocytes with crazy names that protect your body from foreign pathogens.

Now, it may seem as if the disease is only restricted to the mouth. However, periodontal lesions are continually renewing reservoirs for the systemic spread of bacterial antigens, cytokines, and other proinflammatory mediators (5).

In other words, consider a periodontal lesion is like a rotting fruit hidden in the trunk of your car. At first, you have no idea there’s a banana in the trunk under a pile of shoes. However, if left to sit for some time, the once healthy banana will turn into a brown lump of mush. This rotting lump will attract fruit flies just as bacteria in periodontal lesions elicit an immunological response. If the rotting banana is not attended to — like any food that is left out — the smell of decay will permeate the entirety of the car.

Periodontitis and Cardiovascular Disease

Periodontal disease is treatable through surgical procedures that scrape plaque and tartar from teeth and root surfaces. In our rotting fruit analogy, once the source of the smell is found, it can be cleaned away. However, the smell will still remain for quite some time after. This is analogous to the way periopathogenic bacteria can remain in the body via the circulatory system. This can lead to increased risk of certain systemic diseases, including cardiovascular disease.

Consequently, researchers have linked periodontitis to cardiovascular disease. One line of evidence is finding the same species of periodontal pathogens in coronary disease, specifically atherosclerosis. These bacterial species include Porphyromonas gingivalis, Helicobacter pylori, and Prevotella intermedia. Just how these periodontal pathogens lead to thickening of arterial walls is still unknown. However, some researchers propose that, released into the circulation, these microbes can directly invade arterial walls (yuck!). Another proposed pathway is that these pathogens attract inflammatory mediators that produce arterial plaque, early-stage atherosclerosis (4). Additionally, dental treatment procedures may release periodontal pathogens into the systemic circulation.

Periodontitis and Chronic Obstructive Pulmonary Disease

Since the mouth is a gateway to the respiratory tract, it’s easier to see how oral pathogens reach the lungs. In fact, recent epidemiological studies have shown increased risk of chronic obstructive pulmonary disease (COPD) in gum disease patients. This is probably a result of inflammatory responses to certain periodontal pathogens (such as P. gingivalis). There are many shared factors between periodontal disease and COPD. Despite that we still don’t know just how oral bacteria contribute to respiratory infections. However, studies suggest that direct aspiration of oral pathogens into the lungs (yuck!) can cause infection. Alternatively, periodontal disease-associated enzymes in saliva may alter mucosal surfaces, allowing respiratory pathogens to stick more easily (6).

Periodontitis and…Cancer?

If you’re still reading and aren’t floored by all of the information above, get ready for another shocker. Periodontal disease is a risk factor for cancer mortality. (*cue jaw dropping to the floor). This information is based on a 10-year follow up study on 68,273 adults. In particular, this study was seeking a possible connection between periodontal disease and cancer, specifically pancreatic cancer (7). Research on this topic is still in the early stages. However, it stands on the same foundation. It all goes back to bacteria involved in periodontal disease and, ultimately, an imbalanced oral microbiome. Click here to learn more about the oral microbiome and how exactly things spin out of balance.  

Conclusion: Oral microbiome dysbiosis may cause systemic disease!

For those that only read the introduction, conclusion, and skim the rest, this is for you

In conclusion, prevention and early diagnosis of periodontal disease is not only beneficial for oral health, but also for systemic health. This is because periodontal disease is associated with increased risk of cardiovascular disease, COPD and even (tentatively) cancer. But researchers pursue these connections because they better understand of the oral microbiome. The oral microbiome offers a mechanism that explains how mouth diseases contribute to heart, lung and other disease. Continue to the next post to find out how the oral microbiome is associated with specific autoimmune diseases. All in all, good oral health could reduce risk of the diseases mentioned above. More importantly, attention to mouth well-being may improve the well-being of people living with autoimmune diseases.

Written by: Hailey Motooka, Bonnie Feldman, DDS, MBA, Ellen M. Martin

References

1. Bingham, Clifton O., and Malini Moni. “Periodontal Disease and Rheumatoid Arthritis.” Current Opinion in Rheumatology, vol. 25, no. 3, 2013, pp. 345–353., doi:10.1097/bor.0b013e32835fb8ec.
2. Zhang, Xuan, et al. “The Oral and Gut Microbiomes Are Perturbed in Rheumatoid Arthritis and Partly Normalized after Treatment.” Nature Medicine, vol. 21, no. 8, 2015, pp. 895–905., doi:10.1038/nm.3914.
3. Babu, Nchaitanya, and Andreajoan Gomes. “Systemic Manifestations of Oral Diseases.” Journal of Oral and Maxillofacial Pathology, vol. 15, no. 2, 2011, pp. 144–147., doi:10.4103/0973-029x.84477.
4. Bingham, Clifton O., and Malini Moni. “Periodontal Disease and Rheumatoid Arthritis: the Evidence Accumulates for Complex Pathobiologic Interactions.” Current Opinion in Rheumatology, vol. 25, no. 3, 2013, pp. 345–353., doi:10.1097/BOR.0b013e32835fb8ec.
5. Kim, Jemin, and Salomon Amar. “Periodontal Disease and Systemic Conditions: a Bidirectional Relationship.” Odontology, vol. 94, no. 1, 2006, pp. 10–21., doi:10.1007/s10266-006-0060-6.
6. Ramesh, Asha, et al. “Chronic Obstructive Pulmonary Disease and Periodontitis – Unwinding Their Linking Mechanisms.” Journal of Oral Biosciences, vol. 58, no. 1, 2016, pp. 23–26., doi:10.1016/j.job.2015.09.001.
7. Heikkilä, Pia, et al. “Periodontitis and Cancer Mortality: Register‐Based Cohort Study of 68,273 Adults in 10‐Year Follow‐Up.” International Journal of Cancer, vol. 142, no. 11, 11 Jan. 2018, pp. 2244–2253., doi:10.1002/ijc.31254.