Down’s syndrome and hyposalivation: New insights

Dental Tribune International

Fri. 17 July 2026

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NEW YORK, US: Reduced salivary flow is a well-recognised feature of Down’s syndrome and is thought to contribute to the high prevalence of periodontal disease in this patient group. However, the biological mechanisms responsible for hyposalivation have remained unclear. A new preclinical study has investigated the underlying causes, providing fresh insights into why salivary gland function may be impaired in Down’s syndrome.

Using a well-established mouse model, the researchers confirmed reduced salivary flow in the mice and found inflammatory changes within the salivary glands. They linked the reduction in salivary flow to impaired calcium signalling in salivary gland cells, a process essential for saliva secretion. The defect therefore provides a possible biological explanation for hyposalivation. Laboratory-grown human cells derived from an individual with Down’s syndrome also demonstrated reduced calcium signalling, suggesting that this defect may extend beyond the animal model.

Speaking to Dental Tribune International about the motivation for the study, senior author Dr Rodrigo Lacruz, professor of molecular pathobiology at the New York University College of Dentistry, explained: “Many aspects of Down’s syndrome are well documented in the literature. However, a few years ago, the Office of the Surgeon General highlighted the need to investigate oral problems in people with Down’s syndrome. Our review of the literature identified several clinical reports indicating that individuals with Down’s syndrome exhibited hyposalivation and high levels of periodontal disease, which likely go hand in hand. However, the molecular mechanism underlying poor salivation was unknown.”

“Our research group had previously investigated the function of specialised calcium channels in the regulation of salivary secretion in the context of Sjogren’s disease and had shown that calcium signalling is important for salivary secretion. Therefore, we thought that people with Down’s syndrome might also have impaired calcium signalling, potentially leading to hyposalivation and thus periodontitis,” Prof. Lacruz continued.

As reported in the study, the salivary glands also showed evidence of impaired mitochondrial function, which the authors suggest may further compromise salivary secretion. They also identified increased inflammatory activity in the salivary glands and gingival tissue, consistent with previous observations that individuals with Down’s syndrome have heightened immune activation.

“We need to proceed carefully to avoid adversely affecting other systems in people with Down’s syndrome.” — Dr Rodrigo Lacruz

The mice also showed significant alterations in both oral and gut microbial communities. Previous research has demonstrated oral and gut microbiome alterations in people with Down’s syndrome. In the mice, bacteria associated with production of succinate—a metabolic product previously linked to periodontal inflammation—were more abundant, and blood levels of succinate were substantially higher. Together, these findings suggest that hyposalivation, microbial dysbiosis and altered metabolism may interact to drive periodontal disease progression in Down’s syndrome.

The study also explored whether the drug pilocarpine could improve salivary flow in the mice. Treatment significantly improved salivary flow and reduced one of the two gingival inflammatory markers assessed, suggesting that this therapy may warrant further investigation in people with Down’s syndrome.

Commenting on the implications of the pilocarpine findings, Prof. Lacruz stated: “The genetic background associated with Down’s syndrome sets this population apart: over 300 genes on chromosome 21 are overexpressed. These genes may directly or indirectly affect the functioning of genes located on other chromosomes. Pilocarpine may therefore have unintended effects on genes or molecular pathways that may not be affected in individuals with Sjogren’s disease, for example. Therefore, we are investigating other options as well. We need to proceed carefully to avoid adversely affecting other systems in people with Down’s syndrome.”

Although these findings are based on preclinical models, they provide a possible biological explanation for hyposalivation in Down’s syndrome. For dental professionals, the work reinforces the importance of proactive preventive care, regular periodontal monitoring and assessment of salivary function in patients with Down’s syndrome. The findings also highlight potential future therapeutic strategies aimed at improving salivary gland function rather than simply managing its consequences.

The study, titled “Dysregulated calcium signaling underlies hyposalivation and microbial dysbiosis in Down syndrome”, was published online on 1 July 2026 in Cell Reports, ahead of inclusion in an issue.

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Dental research Down's syndrome Hyposalivation Periodontal disease Preventive care

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