This article describes the genesis of oral microbe toxicology, how it impacts health, and how microbial imbalances may lead to immune depletion, autoimmune expression and cancer. The oral microbial ecosystem, better known as the oral microbiome, is particularly important and vital to maintaining both oral and overall health in the body. Salivary flow and biofilms on the teeth and soft tissue maintain microbial equilibrium within the oral cavity and protect pathogens from manifesting and growing. Disturbing the homeostasis of the oral cavity can stir pathogen activity and lead to both oral and systemic disease. Recently, scientists have recognized that oral infection, such as periodontitis, jaw ostitis, non-vital teeth such as root canal-treated teeth, and dental cavitations, may affect the course and pathogenesis of a number of systemic diseases.1, 2, 3, 4 The spread of pathogenic oral microorganisms and their toxins have been implicated in cardiovascular diseases, and numerous neurological and immunological disorders. The interaction between oral and systemic health are bidirectional and complex, involving many biochemical and circulatory pathways.
The number of microbial cells within a human body exceeds the total number of human cells in the body by nearly 10 times.5, 6 Most of these organisms live in the intestine, but more than 700 bacterial species have been detected in the oral cavity.7 The number of bacteria can exceed a thousand billion when the mouth is not sufficiently cleaned. The oral cavity is comprised of many surfaces, each coated with a plethora of bacteria, the proverbial bacterial biofilm. Within the oral cavity, there are two types of surfaces where bacteria can colonize: the hard surfaces of the teeth and jawbone and the soft tissue of the oral mucosa.8 The teeth, gingival sulcus, tongue, cheeks, hard and soft palates, and tonsils each provide enriching environments in which microbial communities can flourish.9
Different types of microorganisms prefer distinct niches according to varying surface structures and functions.10 Each niche provides the optimal conditions and nutrients for its populating microbes.11 Periodontal disease and non-vital teeth, such as root canal-treated teeth, have been established as a source of oral pathogens associated with certain systemic diseases including cancer.12, 13 Studies have also demonstrated that oral bacteria and fungi chronically infect the dentinal tubules and lateral canals of non-vital teeth following a root canal procedure.14 Some microbes that dwell in the mouth readily migrate from the oral cavity, passing with saliva and food into the gastrointestinal tract, or spread into the respiratory mucus membrane system. Oral microbes constitute a "pathogenic reservoir" from which systemic infection and systemic diseases can occur. Dental infections, including gingivitis, periodontitis, dental caries and odontogenic infections, result in numerous dental visits each year. They can range in severity from a mild buccal space infection to a severe life-threatening multi-space infection.
Bacterial toxins and certain species of oral yeast and fungi in the gum or non-vital teeth all produce toxins at sites of active infection.15 These toxins include volatile sulfur compounds, such as hydrogen sulfide (H2S) and methyl-mercaptan (CH3SH) produced from the breakdown of the amino acids cysteine and methionine, respectively, as well as polyamines such as putrescine and cadaverine produced from the breakdown of the amino acids lysine and arginine, respectively. Numerous studies have demonstrated the ability of low micromolar H2S, a known neurotoxin, to inhibit the activity of several vital human enzymes including the Na+/K+-ATPase, cytochrome a3 oxidase, and carbonic anhydrase. When these important metabolic enzymes are depleted, it can lead to compromised immunity and general ill health.
Over 75 different species of oral bacteria have been found to produce significant amounts of hydrogen sulfide. At least 21 different species have been shown to produce methyl mercaptan from degradation of the amino acids cysteine and methionine, respectively.16 Fungal toxins, such as gliotoxin, are thiol-reactive molecules and are damaging to a number of critical metabolic enzymes. Toxin-producing bacteria may also cause cancer by converting ethanol into its carcinogenic derivative, acetaldehyde, to levels capable of inducing DNA damage, mutagenesis, and secondary hyperproliferation of the epithelium. Many oral bacterial and fungal toxins are proven carcinogenic and enter the systemic circulation where they can potentiate carcinogenesis.17, 18 Some of these oral microbes produce toxic nitrosamines that are associated with cancer.
Nitrosation is the process of converting organic compounds into nitroso derivatives, such as nitrosamines. Nitrosamines are a class of chemical compounds first described in the chemical literature over 100 years ago, but which did not receive much attention until 1956. That year, two British researchers, John Barnes and Peter Magee, reported that dimethylnitrosamine produced liver tumors in rats. They proposed that microbial carcinogenesis may also involve nitrosation in which microbial cells catalyze the formation of N-nitroso compounds from the precursor's nitrite and amines, amides, or other nitrosatable compounds. It is now known that several species of oral bacteria encompass strains capable of catalyzing nitrosation.19 Additionally, certain yeasts and fungi that exist in the mouth are nitrosating organisms. Nitrosamine from oral bacteria, yeast, and fungi appears to be a participant in certain carcinomas, not only of the esophagus, but also of other mucosal areas such as the oral cavity.20 Studies continue to emerge linking the toxins of pathogenic oral microorganisms to certain types of cancer.21, 22, 23
Periodontal Disease and Systemic Disease
Periodontal disease is a destructive inflammatory disease of the supporting tissues of the teeth and is caused either by specific microorganisms or by a group of specific microorganisms, resulting in progressive destruction of periodontal ligament and alveolar bone with periodontal pocket formation, gingival recession, or both.24 Periodontal disease is associated with an increased production of reactive oxygen species which, if not buffered sufficiently, cause damage to cells and tissues.25
The spread of oral microorganisms and their toxins have been implicated in cardiovascular disease including heart attack, stroke, high blood pressure, and atherosclerosis, arthritis, implant infections, brain abscesses, hematological infections, and pre-term, low birth weight infants. In particular, a link between periodontal disease and many systemic illnesses such as heart disease, diabetes and stroke has been well documented.26, 27, 28, 29, 30 To date, at least 16 systemic diseases including cancer have been linked to periodontitis. These systemic diseases are associated with periodontal disease because they generally contribute to either a decreased host resistance to infections or dysfunction in the connective tissue of the gums, increasing patient susceptibility to inflammation-induced destruction.31 However, it is important to note that not long ago the idea of periodontal disease causing systemic disorders was considered heresy. Keep this in mind when later reading about the controversy of non-vital, or root canal-treated teeth causing systemic disease.
A 2007 study uncovered a strong correlation of advanced gum disease in men to a 63% higher incidence of pancreatic cancer.32 A year later, another research study confirmed that cancer risk increases when gum disease is present, and that even the presence of moderate gum disease contributed to an overall 14% increased risk of cancer.33 A Swedish study linked periodontal disease to an increased prevalence of breast cancer. Researchers of that study stated that the chronic periodontal disease indicated by missing molars seemed to associate statistically with breast cancer.34 That study puts forward the idea that the risk of a woman developing breast cancer could be amplified by chronic gum disease. The study analyzed and evaluated over 3000 women between the ages of 30 and 40 years over a 16-year period. Among the women studied, those who reported that they had suffered from chronic gum disease or had lost teeth due to periodontal disease were found to be more than two times as likely to be diagnosed with breast cancer as compared to those who had healthy gums.