Scientists have developed a gel that can block the receptor for a molecule called succinate, which is a normal byproduct of metabolism. By blocking its receptor, the gel can lower inflammation levels in the mouth, and alter the community of oral bacteria living there. The work, which used a mouse model and human cells in culture, is the first step on the path to a simple, at-home treatment for gum disease. The work has been published in Cell Reports.
Periodontitis, also known as periodontal or gum disease, is one of the most common inflammatory disorders, and is thought to affect almost half of all people older than 30. There are three hallmarks of gum disease: inflammation, an imbalance or dysbiosis in the oral microbiome, and degradation of the support structures and bones underlying teeth. When gum disease is left untreated, it can cause gums to become painful and bleed. Gum disease patients might have trouble chewing, and may eventually start to lose teeth. Serious gum problems can also interfere with other aspects of health.
Right now, there is not a gum disease treatment that can reduce inflammation, while simultaneously limiting disruption to the oral microbiome and preventing the loss of bone, noted co-first study author Yuqi Guo, an associate research scientist at NYU Dentistry. “There is an urgent public health need for more targeted and effective treatments for this common disease.”
Previous research has indicated that a molecule that is generated during cellular metabolism, called succinate, is associated with gum disease. Higher succinate levels also correspond to higher levels of inflammation. Abnormally high succinate levels were found in human dental plaque. This team has also shown that excess succinate activates its receptor and triggers bone loss. Thus, succinate seemed like a good target to aim for when developing treatments for excessive inflammation, and potentially, gum disease or bone loss.
The researchers engineered mice that lacked the succinate receptor. When gum disease was modeled in these succinate receptor-depleted mice, there was less dysbiosis in their oral microbiomes, and lower levels of inflammation compared to normal mice with gum disease. When mice were exposed directly to succinate, gum disease got worse in normal mice, while the mice without succinate receptors did not experience inflammation, dysbiosis, or bone loss.
Now that the researchers had evidence that high succinate levels can lead to gum disease, and blocking the receptor can relieve it, they formulated a gel containing a succinate receptor-blocking compound.
In a cell culture model, the compound lowered inflammation and other biochemical mechanisms leading to bone loss. When a mouse model of gum disease was treated with the gel, the animals had less inflammation and bone loss compared to mice that did not get the treatment, and within only a few days. There was also a shift in the oral microbiome of the mice. Bacteria called Bacteroidetes, which are dominant during gum disease, were reduced after gel treatment.
However, the investigators determined that the gel was not acting as an antibiotic and was not influencing bacterial growth directly. “This suggests that the gel changes the community of bacteria through regulating inflammation,” suggested co-senior study author Deepak Saxena, a professor at NYU Dentistry.
The researchers want to eventually create gels or oral strips that can be used at home by gum disease patients or those at risk, and a formulation that releases more slowly that can be applied to patches of gum disease.
Sources: New York University, Cell Reports
