The mouth contains one of the most important microbiomes of the human body, housing some 700 different species of bacteria that live in different microbial sub-habitats: teeth, tongue, lip, cheek, hard palate, soft palate, and tonsils. While the mouth is one of the most vital body parts for our health, its significance is often overlooked. In fact, despite my background as a clinical dentist, even I was surprised as I delved into my research on the oral microbiome by many facts about oral health.
The mouth is the first meeting place between our gut (and immune system) and the outside environment: microbes, pathogens, toxins and food nutrients. As the first point of contact, the oral microbiome seeds the rest of the GI tract, with a 45% overlap between the microbes found in the mouth and in the colon (1). However, while high levels of species diversity within the GI tract is correlated with better health, oral disease is associated with higher diversity and richness of microbe species. Good oral health is ensured by maintaining the homeostasis of a relatively limited number of microbe species living within the mouth.
Disturbing the Balance
A new understanding of the oral microbiome is shaping how we think about oral health and disease in relation to some systemic diseases. So far, three pathways linking oral infections to secondary systemic effects have been proposed.
- Metastatic Infection: Transient bacteria from oral infection or dental procedures can gain entrance into the blood and circulate throughout the body. Disseminated microorganisms may find favorable conditions, settle at a given site and start to multiply, colonize and infect the new site.
- Metastatic Injury: Certain bacteria can produce toxins that, when excreted or otherwise introduced into a host body, can trigger many pathological manifestations.
- Metastatic Inflammation: Proinflammatory molecules that enter the bloodstream from oral tissues may react with circulating antibodies to produce large complexes that give rise to acute and chronic inflammatory reactions. (2)
We can gain a more concrete understanding of these mechanisms by looking specifically at the second most common oral disease in the world: periodontal disease–and how periodontitis is connected to cardiovascular disease, chronic obstructive pulmonary disease, and cancer.
Introduction to Periodontal Disease
Periodontal disease refers to inflammatory processes in tissues surrounding the teeth, in response to bacterial accumulations, aka dental plaque, on the teeth (3). When anaerobic bacteria found in invasive microbial plaque penetrate gingival tissues in the gums, this can induce tissue destruction as well as inflammatory responses from cells such as lymphocytes, macrophages, leukocytes, and other cells with crazy names that are associated with the immune system and react to protect your body from foreign pathogens. Now, although it may seem as if the disease is only restricted to the territory of the mouth, periodontal lesions are recognized as continually renewing reservoirs for the systemic spread of bacterial antigens, cytokines, and other proinflammatory mediators (4).
In other words, a periodontal lesion is like a rotting fruit hidden in the trunk of your car. At first, you may have no idea about that old banana sitting in the corner of your trunk underneath a pile of shoes. However, if left to sit, the once healthy banana will turn into a brown lump of mush that will attract fruit flies, in the same way the bacteria in periodontal lesions elicit an immunological response. If the rotting banana is still not attended to, then the normal progression of any food item that is left out will follow, and the smell of decay will inevitably permeate the entirety of the car.
Periodontitis and Cardiovascular Disease
Periodontal disease itself is treatable through surgical procedures that involve removing plaque and tartar from the teeth and root surfaces. Relating back to the rotting fruit analogy, once the source of the smell is found, it too, can be cleaned and managed. However, the smell will still remain for quite some time after, similarly to the way periopathogenic bacteria will remain in the body due to dissemination via the circulatory system. This can lead to increased risk of certain systemic diseases, including cardiovascular disease, as well as prompt reinfection of the gums.
Researchers have linked periodontitis to cardiovascular disease through corroborating associations between specific bacteria (consistent with periodontitis) and coronary diseases developing as a result of atherosclerosis. The exact mechanism in which pathogenic bacteria involved in periodontal disease (such as Porphyromonas gingivalis, Helicobacter pylori, and Prevotella intermedia) influence thickening of arterial walls is still in the hypotheses stage, but it is proposed that migration of such microbes into the circulation system can lead to a direct invasion of arterial walls. Another proposed pathway is the release, in response to infection, of systemic inflammatory mediators that produce arterial plaque, the early stages of atherosclerosis (3). Periodontal pathogens can also spread into the systemic circulation system by means of dental treatment procedures that allow them to pass directly into the bloodstream.
Periodontitis and Chronic Obstructive Pulmonary Disease
Due to the close proximity and crucial role of the oral cavity to the respiratory tract, perhaps it is easier to see how pathogens in the mouth can affect the lungs rather than the heart. In fact, recent epidemiological studies have shown that there is an increased risk of chronic obstructive pulmonary disease (COPD) as a result of inflammatory responses to certain periodontal pathogens (such as P. gingivalis). Despite the numerous shared associations between periodontal disease and COPD, the exact mechanism by which oral bacteria contribute to the pathogenesis of respiratory infections is still unknown. However, studies have suggested that either direct aspiration of oral pathogens into the lungs can cause infection, or periodontal disease-associated enzymes in saliva can alter mucosal surfaces, promoting adhesion of respiratory pathogens further down in the trachea and lungs (5).
Periodontitis and Cancer
A recent follow-up study (over the course of 10 years) was conducted on 68,273 adults in order to determine a possible connection between periodontal disease and cancer, particularly pancreatic cancer (6). The results found that periodontal disease is an associated risk factor for cancer mortality (specifically pancreatic cancer). Research on this topic is still in the early stages, but the basis on which it stands still traces back to bacteria involved in periodontal disease and, ultimately, an imbalanced oral microbiome.
- Segata, Nicola, et al. “Composition of the Adult Digestive Tract Bacterial Microbiome Based on Seven Mouth Surfaces, Tonsils, Throat and Stool Samples.” Genome Biology, vol. 13, no. 6, 2012, doi:10.1186/gb-2012-13-6-r42.
- 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.
- 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.
- 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.
- 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.
- 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.