Loss of the disease-associated glycosyltransferase Galnt3 alters Muc10 glycosylation and the composition of the oral microbiome

The importance of the microbiome in health and its disruption in disease is continuing to be elucidated. However, the multitude of host and environmental factors that influence the microbiome are still largely unknown. Here, we examined UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase 3 (Galnt3)-deficient mice, which serve as a model for the disease hyperphosphatemic familial tumoral calcinosis (HFTC). In HFTC, loss of GALNT3 activity in the bone is thought to lead to altered glycosylation of the phosphate-regulating hormone fibroblast growth factor 23 (FGF23), resulting in hyperphosphatemia and subdermal calcified tumors. However, GALNT3 is expressed in other tissues in addition to bone, suggesting that systemic loss could result in other pathologies. Using semiquantitative real-time PCR, we found that Galnt3 is the major O-glycosyltransferase expressed in the secretory cells of salivary glands. Additionally, 16S rRNA gene sequencing revealed that the loss of Galnt3 resulted in changes in the structure, composition, and stability of the oral microbiome. Moreover, we identified the major secreted salivary mucin, Muc10, as an in vivo substrate of Galnt3. Given that mucins and their O-glycans are known to interact with various microbes, our results suggest that loss of Galnt3 decreases glycosylation of Muc10, which alters the composition and stability of the oral microbiome. Considering that oral findings have been documented in HFTC patients, our study suggests that investigating GALNT3-mediated changes in the oral microbiome may be warranted.

Reduced Salivary Mucin Binding and Glycosylation in Older Adults Influences Taste in an In Vitro Cell Model

Background: Taste loss is a significant problem in older adults, affecting quality of life and nutrition. Altered salivary rheology and loss of mucin function may contribute to taste loss by reducing mucosal defences in the oral cavity, impairing sensitivity to oral stimulants. This study aimed to investigate the effects of salivary rheology on taste loss in ageing. Salivary mucin glycosylation and binding to the oral epithelium was investigated in older and younger adults. A cell-based model was utilised to consider the role of saliva in taste loss. Methods: Human subjects aged >60 years (n = 25) and 18–30 (n = 30) provided saliva samples which were analysed for viscosity, mucin composition and mucin binding to oral epithelial cells (TR146/MUC1). Oral epithelial cells (TR146/MUC1 and SCC090) provided models for taste receptor activation. Results: Reduced levels and sialylation of MUC7 were evident in saliva of older adults which may lead to reduced viscoelasticity, while viscosity is unaffected. Impaired muco-adhesion of saliva from older adults was also observed. Saliva from older adults facilitated the bitter taste receptor activation less well than saliva from younger adults. The causes of taste dysfunction in older adults are unknown, but this study supports a role of saliva in facilitating the activation of taste receptors.