A compelling new study is claiming to have uncovered the missing link explaining how gum disease is associated with diabetes, cardiovascular disease and even Alzheimer’s. The research demonstrates how periodontitis can initiate a systemic immune response that spreads hyperactive inflammatory cells throughout the entire body.
Severe periodontitis, or gum disease, has long been observationally associated with broader systemic diseases. Links between bad oral health and hypertension or even Alzheimer’s disease have frequently been detected but it has been challenging to determine whether the relationship is causal.
Now, in a robust study led by researchers from the University of Toronto, a potential mechanism has been found illustrating how oral disease may be exacerbating these other inflammatory conditions.
The researchers set out to explore the activity of a type of immune cell known as neutrophils. These frontline immune cells are produced when the body senses infection or trauma. And in the case of gum disease, neutrophils are a key part of the body’s natural immune response.
Initially using a mouse model of periodontitis, the researchers found an acute oral infection rapidly leads to heightened neutrophil production, and not just in the mouth. The animal model revealed increased neutrophil activity was detected in the bloodstream and colon, as well as the mouth. Elevated neutrophil counts were also seen in the animals’ bone marrow, suggesting the oral infection may be triggering broader systemic production of these immune cells.
Michael Glogauer, senior author on the new study, says these heightened levels of neutrophils then circulate throughout the body, primed to attack any secondary infection. And this mechanism could be triggering, or at least exacerbating, other inflammatory conditions.
“It’s almost as if these white blood cells are in second gear when should be in first,” says Glogauer. “The [neutrophils] are much more likely to release cytokines much more quickly, leading to negative outcomes.”
The second part of the study looked to verify this kind of enhanced neutrophil activity in humans. A small cohort of volunteers was recruited and directed to stop brushing their teeth for three weeks in order to stimulate gingivitis, or inflammation of the gums.
After three weeks the researchers confirmed, through a variety of tests, enhanced systemic neutrophil activity. These abnormal immune markers disappeared two weeks after the subjects resumed their regular oral hygiene behaviors.
“We believe this is the mechanism by which oral hygiene can impact vulnerability to unrelated secondary health challenges,” says lead author Noah Fine. “Neutrophil (immune) priming throughout the body can connect these seemingly distinct conditions.”
Interestingly, the researchers suggest this discovery may help explain why some recent studies have cited connections between COVID-19 complications and poor oral health. Hyperactive immune system activity, referred to as cytokine storms, has been implicated in severe COVID-19 cases leading to death. Glogauer hypothesizes gum disease amplifying neutrophil activity may play a role increasing a person’s risk for severe COVID-19.
“There is evidence out there that patients with periodontal disease may be much more likely to have negative outcomes with COVID-19,” says Glogauer. “Neutrophils are the cells that are at prime risk of causing cytokine storms. That’s the exact cell we show is primed with people with periodontal disease.”
The new study was published in The Journal of Dental Research .