Unlike Las Vegas, “what happens in the mouth doesn’t stay in the mouth.” Like hooligans jumping turnstiles and hitching free rides out of town on a subway, pathogens and problematic compounds that originate in or are mainly found in the oral cavity may make their way to other parts of the body and contribute to compromised health in those areas.
One of the better-known connections here is between dental plaque and atherosclerotic plaque. In fact, according to data from the National Health and Nutrition Examination Survey (NHANES III), individuals with severe periodontal disease had a nearly four times higher incidence of myocardial infarction than individuals free of periodontal disease. The simplest explanation for this is that people who neglect their oral health may also neglect other aspects of their health, so it’s not unusual for there to appear to be associations between seemingly unrelated issues. However, as is so often true in medicine, things are rarely as simple as we might think.
It’s possible that an inflammatory reaction in the oral cavity “may potentiate the atherosclerotic process by stimulation of humoral and cell-mediated inflammatory pathways,” with severe periodontal disease inducing inflammation sufficient to trigger systemic inflammation. Moreover, “the presence of periodontal infection may lead to brief episodes of bacteremia with inoculation of atherosclerotic plaques by periodontal pathogens such as Porphyromonas gingivalis, Actinobacillus actinomycetemcomitans, and Bacteroides forsythus. Subsequent growth of these bacteria would cause inflammation and plaque instability. Indeed, there is evidence using immunostaining and polymerase chain reaction for bacterial rDNA that these pathogens are present in 18% to 30% of carotid atheromas.” That’s right—oral cavity pathogens winding up in the carotid artery. Like we said: what happens in the mouth…
If these bacteria can migrate to the cardiovascular system, might they also wreak havoc in other parts of the body? Maybe in the joints? In the case of Porphyromonas gingivalis, the answer is yes. P. gingivalis is a gram-negative anaerobic bacterium, and the major pathogen contributing to chronic periodontitis. It is increasingly recognized that oral infections and periodontitis play a role in the development of rheumatoid arthritis (RA). And this isn’t just a mere association. It seems that P. gingivalis may actually be a causal factor in “initiating, amplifying and perpetuating” RA.
How is this possible? How could an oral pathogen trigger an autoimmune attack on joint tissue? P. gingivalis produces the enzyme peptidyl arginine deiminase 4 (PAD4), which mediates the citrullination of proteins such as collagen and fibrinogen. Antibodies to citrullinated proteins are a hallmark of RA. In addition to auto-citrullinating, P. gingivalis can mediate the modification of host proteins associated with joint structures, potentially resulting in RA via molecular mimicry.
Researchers note that antibodies to citrullinated proteins “that are highly specific for RA are detectable years before disease development.” The proliferation of P. gingivalis could be “the straw that breaks the camel’s back” and leads to the loss of immune tolerance to these proteins. It’s also possible that signs and symptoms of RA don’t manifest until joint damage crosses a certain threshold, but by the time this happens, P. gingivalis “infestation” has already been in place for a significant period of time. Either way, it seems there’s a genetic component involved, and these processes are more likely to trigger RA in those with genetic susceptibility.
P. gingivalis is the only human pathogen currently known to express the PAD4 enzyme, and this organism has direct effects on apoptosis of human chondrocytes, which would have obvious ramifications for joint health. The authors of a study that analyzed the effects of P. gingivalis on human chondrocytes in vitro stated it clearly: “P. gingivalis promotes early and later stages of apoptosis of primary human chondrocytes, which might contribute to the joint damage seen in the pathogenesis of RA.”
Several studies corroborate the NHANES III finding of increased incidence of RA in individuals with periodontitis. A small case/control study determined that after factoring in age, RA status, gender, education, smoking, alcohol consumption, and BMI, only RA status and age remained significant predictors of periodontal disease. Subjects with RA had an approximately 8-fold increase in periodontitis incidence compared to controls. This is especially revealing, because it rules out some (although not all) of the confounding factors we might otherwise attribute the association to—especially smoking, alcohol consumption, and BMI.
For people looking to take a risk, the poker table or roulette wheel might be a better choice than neglecting oral hygiene—or better yet, a lottery ticket. No one should gamble with their joints.