First-ever oral gel treats and prevents gum disease
[Mar. 26, 2023: RS Shavit, The Brighter Side of News]
The research 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. (CREDIT: Creative Commons)
NYU College of Dentistry researchers have discovered a novel treatment for gum disease that targets a metabolic byproduct called succinate. The team published a study in Cell Reports that demonstrated a topical gel formulated to block the succinate receptor can suppress inflammation, alter the microbiome in the mouth, and treat gum disease in mice.
Gum disease, also known as periodontitis, is a prevalent inflammatory disease that affects nearly half of adults 30 years and older. It has three components: inflammation, an imbalance of unhealthy and healthy bacteria in the mouth, and destruction of the bones and structures that support the teeth. Uncontrolled gum disease can lead to painful and bleeding gums, difficulty chewing, and tooth loss.
The researchers discovered that increased succinate is linked to gum disease, with higher levels associated with higher levels of inflammation. Elevated levels of succinate activate the succinate receptor and stimulate bone loss, making the receptor an appealing target for countering inflammation and bone loss.
The researchers examined dental plaque samples from humans and plasma samples from mice, finding higher succinate levels in people and mice with gum disease compared to those with healthy gums. The succinate receptor was expressed in human and mouse gums.
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They genetically altered mice to inactivate the succinate receptor, finding “knockout” mice with gum disease had lower levels of inflammation in the gum tissue and blood and less bone loss.
“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,” said Deepak Saxena, professor of molecular pathobiology at NYU Dentistry and the study’s co-senior author.
“Mice without active succinate receptors were more resilient to disease,” said Fangxi Xu, an assistant research scientist in the Department of Molecular Pathobiology at NYU Dentistry and the study’s co-first author. “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.”
A topical gel that blocks the receptor for a metabolic byproduct called succinate treats gum disease by suppressing inflammation and changing the makeup of bacteria in the mouth. (CREDIT: Yuqi Guo)
The researchers then developed a gel formulation of a small compound that targets the succinate receptor and prevents it from being activated. The compound reduced inflammation and processes that lead to bone loss when laboratory studies of human gum cells were conducted.
The compound was then applied as a topical gel to the gums of mice with gum disease, reducing local and systemic inflammation and bone loss in a matter of days. The researchers applied the gel to the gums of mice with gum disease every other day for four weeks, which halved their bone loss compared to mice who did not receive the gel.
Graphical abstract: Targeting the succinate receptor effectively inhibits periodontitis. (CREDIT: Cell Reports)
Mice treated with the gel had significant changes to the community of bacteria in their mouths. Notably, bacteria in the Bacteroidetes family that include pathogens known to be dominant in gum disease were depleted in those treated with the gel.
The gel is undergoing additional tests to find the appropriate dosage and timing for application, as well as determine any toxicity. The 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.
SUCNR1 KO mice are resistant to bone loss, inflammation, and dysbiosis induced by periodontitis. (CREDIT: Cell Reports)
“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 at NYU Dentistry and the study’s lead author.
Additional study authors include Scott Thomas, Yanli Zhang, Bidisha Paul, Sungpil Chae, Patty Li, Caleb Almeter, and Angela Kamer of NYU Dentistry; Satish Sakilam and Paramjit Arora of NYU Department of Chemistry; and Dana Graves of the University of Pennsylvania School of Dental Medicine.
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