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J. Mol. Sci.","IJMS"],"abstract":"<jats:p>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 \u03b12-3 sialylated glycan structures (SA\u03b12-3Gal) 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 \u03b12,3-DeSia-GP) were prepared from bovine milk-derived glycoproteins to investigate the functional contribution of SA\u03b12-3Gal. 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 \u03b12-3-linked sialic acids, demonstrating the essential role of SA\u03b12-3Gal. 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 SA\u03b12-3Gal 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\u2013microbe interactions and suggests that the naturally low abundance of SA\u03b12-3Gal in children may increase their susceptibility to S. mutans infection and caries development.<\/jats:p>","DOI":"10.3390\/ijms27156562","type":"journal-article","created":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T17:13:17Z","timestamp":1784826797000},"page":"6562","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["\u03b12-3-Sialylated Glycoproteins Attenuate Streptococcus mutans Virulence and Associated Host Inflammatory Responses"],"prefix":"10.3390","volume":"27","author":[{"given":"Xiameng","family":"Ren","sequence":"first","affiliation":[{"name":"Laboratory for Functional Glycomics, Faculty of Life Science & Medicine, Northwest University, Xi\u2019an 710069, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingyun","family":"Wei","sequence":"additional","affiliation":[{"name":"Laboratory for Functional Glycomics, Faculty of Life Science & Medicine, Northwest University, Xi\u2019an 710069, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Medicine, Faculty of Life Science & Medicine, Northwest University, Xi\u2019an 710069, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Wang","sequence":"additional","affiliation":[{"name":"Laboratory for Functional Glycomics, Faculty of Life Science & Medicine, Northwest University, Xi\u2019an 710069, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyi","family":"Chang","sequence":"additional","affiliation":[{"name":"Laboratory for Functional Glycomics, Faculty of Life Science & Medicine, Northwest University, Xi\u2019an 710069, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Shu","sequence":"additional","affiliation":[{"name":"School of Medicine, Faculty of Life Science & Medicine, Northwest University, Xi\u2019an 710069, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1839-3450","authenticated-orcid":false,"given":"Zheng","family":"Li","sequence":"additional","affiliation":[{"name":"Laboratory for Functional Glycomics, Faculty of Life Science & Medicine, Northwest University, Xi\u2019an 710069, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.cell.2014.03.011","article-title":"Role of the microbiota in immunity and inflammation","volume":"157","author":"Belkaid","year":"2014","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1093\/glycob\/cww086","article-title":"Biological roles of glycans","volume":"27","author":"Varki","year":"2016","journal-title":"Glycobiology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.tim.2011.10.001","article-title":"Microbial adhesins to gastrointestinal mucus","volume":"20","author":"Juge","year":"2012","journal-title":"Trends Microbiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"136932","DOI":"10.1016\/j.ijbiomac.2024.136932","article-title":"Glycans in the oral bacteria and fungi: Shaping host-microbe interactions and human health","volume":"282","author":"Ren","year":"2024","journal-title":"Int. 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