Abstract

Glycans attached to host glycoproteins play an important role in regulating oral microbial colonization and maintaining community balance. Our previous studies revealed that children exhibit lower levels of α2-3 sialylated glycan structures (SAα2-3Gal) than adults, raising the possibility that this age-associated glycan deficiency contributes to the heightened cariogenicity of Streptococcus mutans . In this study, sialylated glycoproteins (Sia-GP) and corresponding desialylated controls (DeSia-GP and α2,3-DeSia-GP) were prepared from bovine milk-derived glycoproteins to investigate the functional contribution of SAα2-3Gal. Their effects on S. mutans were evaluated by assessing bacterial growth, acid production, biofilm formation and extracellular polysaccharide synthesis, while a human oral keratinocytes (HOK cells) infection model was used to examine epithelial cell viability, wound healing, and infection-associated inflammatory responses. The results showed that Sia-GP exerted only a transient inhibitory effect on early bacterial growth without affecting final biomass, but significantly attenuated acidogenic activity, biofilm formation, and extracellular polysaccharides production in a concentration-dependent manner. These inhibitory effects were markedly attenuated following removal of α2-3-linked sialic acids, demonstrating the essential role of SAα2-3Gal. In addition, Sia-GP alleviated S. mutans -induced cellular damage in HOK cells by improving cell viability, colony formation, and migration, while suppressing infection-associated inflammatory signaling. Collectively, these findings demonstrate that SAα2-3Gal effectively limits multiple virulence traits of S. mutans and attenuates S. mutans -induced damage in oral epithelial cells. This study provides mechanistic insights into glycan-mediated regulation of host–microbe interactions and suggests that the naturally low abundance of SAα2-3Gal in children may increase their susceptibility to S. mutans in