A newly discovered gel that can be applied topically appears to block the receptor for a common pro-inflammatory protein called succinate that is regularly found in our bodies. A new study led by researchers at NYU College of Dentistry and published in Cell Reports has shown that by blocking this receptor it suppresses inflammation of the gums and suppresses gum disease (also known as periodontitis or periodontal disease). What is even more fascinating, is that by suppressing inflammation it has been shown to change the makeup of bacteria in the mouth.
The research, conducted in mice and using human cells and plaque samples, lays the groundwork for a non-invasive treatment for gum disease that people could apply to the gums at home to prevent or treat gum disease.
Periodontitis, and its cousin “peri-implantitis” (gum disease that affects dental implants) is one of the most widespread inflammatory conditions which affects nearly 50% of adults over the age of 30. The hallmark features of both types of gum disease is marked by three components: inflammation, a shift towards “periodontopathogenic” bacteria in the mouth (unhealthy bacteria), and destruction of the bones and structures that support teeth and dental implants. Uncontrolled gum disease can lead to painful and bleeding gums, difficulty chewing, and tooth or implant loss.
“No current treatment for gum disease simultaneously reduces inflammation, limits disruption to the oral microbiome, and prevents bone loss. There is an urgent public health need for more targeted and effective treatments for this common disease,” said the study’s author Yuqi Guo, an associate research scientist in the Department of Molecular Pathobiology at NYU Dentistry. Past research has linked a naturally occurring byproduct called succinate to gum disease. The higher succinate levels in our blood and saliva were associated with higher levels of inflammation. Guo and her colleagues at NYU Dentistry also discovered in 2017 that bone loss around teeth and dental implants was stimulated as more succinate receptors became activated by increasing levels of succinate.
This discovery made targeting the succinate receptor central to the fight against inflammation thereby potentially stopping bone loss and gum disease in its tracks.
The research publication shows that “Mice without active succinate receptors were more resistant to periodontal disease,”. The authors continue to say that “While we already knew that there was some connection between succinate and gum disease, we now have stronger evidence that elevated succinate and the succinate receptor are major drivers of the disease.” The researchers then developed a compound that could target the succinate receptor just by being absorbed through the gums. In-situ trials showed that the topical ointment reduced inflammation and bone loss.
The compound was then applied topically to the gums of mice with gum disease, which reduced local and systemic inflammation and bone loss in a matter of days. In one test, the researchers applied the gel to the gums of mice with gum disease every other day for four weeks, which cut their bone loss in half compared to mice who did not receive the gel.
Mice treated with the gel also had significant changes to the types of bacteria in their mouths. Specifically, bacteria in the Bacteroidetes family—which include pathogens that are known to be dominant in gum disease—were depleted in those treated with the gel.
“We conducted additional tests to see if the compound itself acted as an antibiotic and found that it does not directly affect the growth of bacteria. This suggests that the gel changes the community of bacteria through regulating inflammation without the risk of creating resistant bacterial strains,” said Deepak Saxena, professor of molecular pathobiology at NYU Dentistry.
The researchers are continuing to study the gel in animal models to find the appropriate dosage and timing for application, as well as determine any toxicity. Their long-term goal is to develop a gel and oral strip that can be used at home by people with or at risk for gum disease, as well as a stronger, slow-release formulation that dentists can apply to pockets that form in the gums during gum disease.
“Current treatments for severe gum disease can be invasive and painful. In the case of antibiotics, which may help temporarily, they kill both good and bad bacteria, disrupting the oral microbiome. This new compound that blocks the succinate receptor has clear therapeutic value for treating gum disease using more targeted and convenient processes,” said Xin Li, professor of molecular pathobiology at NYU Dentistry and the study’s lead author.