Mechanism Connecting Periodontitis With Other Inflammatory Diseases Uncovered

Dentistry Today
Credit: Noah Fine


Credit: Noah Fine

The link between periodontal disease and other inflammatory conditions such as heart disease and diabetes has long been established. But the mechanism behind that association has been a mystery until now, as researchers at the University of Toronto Faculty of Dentistry say it has to do with the body’s own hyperactive immune response.

Science has already established that oral health is an important indicator of overall health, the researchers said.

“There are statistically significant correlations between periodontitis (oral inflammatory disease) and systemic diseases ranging from diabetes to cardiovascular diseases,” said Howard Tenenbaum, DDS, PhD, professor with the Faculty of Dentistry, chief dentist at Sinai Health Systems in Toronto, and one of the authors of the study.

To find what links those conditions, the researchers focused on the behaviors of cells primarily activated by gum disease, neutrophils, which are cells of the innate immune system. Through in vivo models, the researchers found that the immune system releases an abundance of these neutrophils to tackle the bacterial infections responsible for periodontitis.

Activated to fight an oral infection, a systemic effect was noted. Once periodontal inflammation was present, an overabundance of neutrophils circulated, “primed” for attack, the researchers said. The hyper-vigilant immune system then responds with an excess of force to any secondary infection.

“It’s almost as if these white blood cells are in second gear when they should be in first,” said Michael Glogauer, DDS, PhD, Dip Perio, professor with the Faculty of Dentistry and the study’s senior author.

That’s when the body becomes susceptible to damage from secondary inflammatory conditions. With the immune system already primed by the neutrophils for attack, a secondary event causes those immune cells to destroy affected tissues and organs.

“The [neutrophils] are much more likely to release cytokines much more quickly, leading to negative outcomes,” said Glogauer, who also is dentist in chief at the University Health Network and head of dental oncology at Toronto’s Princess Margaret Cancer Centre.

Produced initially in in vivo models, the findings were confirmed through a controlled clinical experiment. These findings underscore the importance of oral health as a vital indicator of potential complications for other inflammatory conditions as well as disease model outcomes, the researchers said.

“We believe this is the mechanism by which oral hygiene can impact vulnerability to unrelated secondary health challenges,” said lead author Noah Fine, a postdoctoral fellow with the Faculty of Dentistry. “Neutrophil (immune) priming throughout the body can connect these seemingly distinct conditions.”

The study also may have important ramifications for another inflammatory disease, COVID-19, the researchers said.

“There is evidence out there that patients with periodontal disease may be much more likely to  have negative outcomes with COVID-19,” said 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.”

Research into the relationship between neutrophils and inflammation is ongoing.

The study, “Periodontal Inflammation Primes the Systemic Innate Immune Response,” was published by the Journal of Dental Research.

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