Researchers at NYU have identified why people with Down syndrome are at dramatically higher risk for severe gum disease, uncovering a molecular mechanism involving calcium signaling and reduced saliva production that could lead to new treatments. An estimated 60 to 90 percent of individuals with Down syndrome develop periodontal disease before age 35, a rate far exceeding that of people without Down syndrome, including those with other intellectual disabilities.

What Makes Oral Health Different for People With Down Syndrome?

The newly published study in Cell Reports, conducted by researchers at NYU College of Dentistry, addresses what scientists describe as a largely overlooked aspect of Down syndrome. According to the United Nations, Down syndrome occurs in approximately one in every 1,000 to 1,100 live births worldwide, with an estimated 3,000 to 5,000 children born with the condition each year.

The research team discovered that people with Down syndrome produce significantly less saliva, a condition known as hyposalivation. This reduced saliva disrupts the oral microbiome, allowing disease-causing bacteria to flourish and increasing the risk of gum disease and tooth decay. The findings also suggest that poor oral health may contribute to other health problems, including Alzheimer's disease, which affects many people with Down syndrome as they age.

"Understanding the processes responsible for low saliva in Down syndrome and developing therapies to restore salivation could have a transformative impact on the oral and overall health of people with Down syndrome," said Rodrigo Lacruz, professor of molecular pathobiology at NYU College of Dentistry and the study's senior author.

Rodrigo Lacruz, Professor of Molecular Pathobiology, NYU College of Dentistry

How Does Calcium Signaling Affect Saliva Production?

To understand the biology behind these oral health issues, researchers studied a widely used mouse model of Down syndrome. Like people with the condition, the mice produced significantly less saliva. Their saliva was also more acidic and contained higher levels of certain immune markers.

The key finding involved a process called store-operated calcium entry, which is essential for saliva secretion. Researchers found that this calcium signaling process was impaired in the salivary glands of the mice with Down syndrome. The team also detected increased inflammation in gum tissue, along with decreased mitochondrial function in the salivary glands.

"This dysfunction in calcium signaling is likely responsible for hyposalivation in Down syndrome. Decreased saliva flow can have systemic consequences, advancing periodontal disease and impacting the microbial ecosystem," explained Lacruz.

Rodrigo Lacruz, Professor of Molecular Pathobiology, NYU College of Dentistry

Additional analyses revealed elevated levels of succinate, a metabolic byproduct linked to inflammation and gum disease, in the blood, along with succinate-producing bacteria in both the gut and oral microbiome. The researchers also detected autoantibodies associated with Sjögren's disease, an autoimmune disorder that affects the salivary glands, suggesting that people with Down syndrome may be at increased risk of developing this condition.

Steps to Support Oral Health in People With Down Syndrome

• Increase Dental Visit Frequency: More frequent dental visits beyond standard recommendations can help catch and treat gum disease early before it becomes severe.
• Optimize Diet and Brushing Practices: Dietary modifications and improved toothbrushing techniques, particularly in group home settings, can reduce bacterial buildup and plaque formation.
• Consider Saliva-Stimulating Medications: Pilocarpine, a medication used to stimulate saliva production, increased salivation in the research mice and may offer therapeutic potential for people with Down syndrome.

What's Next for Treatment?

The researchers found that Pilocarpine, a medication already used to stimulate saliva production, increased salivation in the mice. This finding suggests that targeting hyposalivation could one day help improve both oral and systemic health in people with Down syndrome.

"Targeting hyposalivation to boost saliva production could potentially improve some of the systemic disruptions that individuals with Down syndrome experience. This is our next research focus," stated Lacruz.

Rodrigo Lacruz, Professor of Molecular Pathobiology, NYU College of Dentistry

The study emphasizes that while dietary and oral hygiene factors may contribute to dental issues in some people with Down syndrome, the underlying biological changes in saliva, calcium signaling, and the microbiome are critical factors that must be addressed. Researchers note that the systemic alterations of succinate and changes to the oral and gut microbiome appear to be influencing the broader biology of Down syndrome, suggesting that improving oral health could have far-reaching effects on overall wellness.

This research represents a significant step forward in understanding why people with Down syndrome face such high rates of gum disease and opens the door to targeted therapies that could transform both their oral and systemic health outcomes.