A new study led by researchers at the New York University School of Dentistry reports that a topical gel that blocks the receptors for a metabolic byproduct called succinate treats gum disease by inhibiting inflammation and altering the composition of bacteria in the mouth. Posted in cell reports.
The research, conducted in mice and using human cells and plaque samples, lays the foundation for a non-invasive treatment of gum disease that people can apply to their gums at home to prevent or treat gum disease.
Periodontal disease (also known as periodontitis or periodontal disease) is one of the most common inflammatory diseases, Affect nearly half of adults 30 and over. It is characterized by three components: inflammation, an imbalance of healthy and unhealthy bacteria in the mouth, and the destruction of the bones and structures that support the teeth. Uncontrolled gum disease can lead to Painful gums, bleeding, difficulty chewing, and tooth loss.
“No current treatment for periodontal disease simultaneously reduces inflammation, limits disruption of the oral microbiome, and prevents bone loss,” said Yuki Jo, associate research scientist in the New York University Department of Dental Molecular Pathology and co-first author of the study. general public for more targeted and effective treatments for this common disease.
Previous research has linked increased succinate – a molecule produced during metabolism – and gum disease, with higher sugar levels linked to higher levels of inflammation. Guo and her colleagues at the New York University School of Dentistry, too Discovered in 2017 High levels of succinate activate succinate receptors and stimulate bone loss. These findings make succinate receptors an attractive target for counteracting inflammation and bone loss — and possibly stopping gum disease in its tracks.
Strengthening the association between succinate and periodontal disease
The researchers began by examining plaque samples from humans and plasma samples from mice. Using metabolic analyses, they found higher levels of succinate in people and mice with periodontal disease than in those with healthy gums, confirming previous studies.
They also saw that succinate receptors are expressed in human and mouse gums. To test the link between succinate receptors and components of periodontal disease, they genetically altered mice to deactivate or “disable” the succinate receptor.
In mice with periodontal disease, the researchers measured lower levels of inflammation in both gum tissue and blood, as well as less bone loss. They also found different bacteria in their mouths: mice with periodontal disease had greater bacterial imbalances than mice with periodontal disease.
This was true when the researchers administered more succinate to both types of mice, which exacerbated gum disease in normal mice. However, the “knockout” mice were protected from infections, an increase in unhealthy bacteria, and bone loss.
“Mice without active succinate receptors were more resistant to disease,” said Fangxi Xu, an assistant researcher in the Department of Dental Molecular Pathology at New York University and co-first author of the study. “While we already knew there was some link between succinate and periodontal disease, we now have stronger evidence that hyperglycemia and succinate receptors are the main drivers of the disease.”
To see if blocking the succinate receptor can alleviate gum disease, researchers developed a gel formulation of a small compound that targets the succinate receptor and prevents its activation. In laboratory studies human gum cellsThe compound reduces inflammation and processes that lead to bone loss.
The compound was then applied as a topical gel to the gums of mice with periodontal disease, which reduced local and systemic inflammation and bone loss within days. In one test, researchers applied the gel to the gums of mice with periodontal disease every two days for four weeks, which cut bone loss in half compared to mice who didn’t get the gel.
The mice treated with the gel also had significant changes in the bacterial community in their mouths. It is worth noting that the bacteria present in germs The family–which includes pathogens known to be prevalent in periodontal disease–was depleted in those treated with the gel.
We ran additional tests to see if the same compound worked as an antibiotic, and found that it didn’t directly affect bacterial growth. This suggests that the gel alters the bacteria community by regulating inflammation,” said Deepak Saxena, a professor at New York University Dental School and co-author of the study.
Researchers continue to study the gel in animal models to find the appropriate dose and timing of application, as well as to determine any toxicity. Their long-term goal is to develop an oral gel and strip that can be used at home by people with or at risk of gum disease, as well as a stronger slow-release formula that dentists can apply to pockets that form in the gums during periodontal 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. Shen Li, professor of dentistry at New York University and lead author of the study, said This new succinate receptor-blocking compound has a clear therapeutic value for treating periodontal disease using more targeted and appropriate procedures.
Additional study authors include Scott Thomas, Yanli Zhang, Pedicha Paul, Songpil Chai, Patti Lee, Caleb Almeter and Angela Kamer of New York University School of Dentistry. Satish Sakilam and Paramjit Arora from New York University’s Department of Chemistry; and Dana Graves of the University of Pennsylvania School of Dentistry.
The research was supported by the National Institutes of Health (DE027074, DE028212, AG068857, and R01DE017732); The Develop gel and oral strip Funded by the National Dental and Craniofacial Research Institute (R41DE028212). Lee and Saxena are co-founders of Periomics Care, an early-stage biotechnology company within New York University dentistry.
About the New York University School of Dentistry
Founded in 1865, NYU Dentistry is the third oldest and largest dental college in the United States, with nearly 10% of the nation’s dentists educated. NYU Dentistry has a significant global reach with a highly diverse student body.
visit Dental.nyu.edu For more.