Roles of Intestinal Epithelial Glycans in Maintaining Gut Homeostasis

Glycans expressed by intestinal epithelial cells, particularly O-linked glycans on mucins, play critical roles in maintaining the mucosal barrier and regulating the gut microbiota. These glycans support the polymerization and viscosity of mucins, forming a protective mucus layer that prevents bacterial invasion. Specific glycan structures, including fucosylated, sialylated, and sulfated glycans, vary by intestinal region and are essential for mucus integrity. Glycosyltransferase-deficient mice have revealed that disruption of these glycans compromises barrier function and increases susceptibility to intestinal inflammation. Additionally, host glycans serve as nutrient sources for commensal bacteria, such as Akkermansia muciniphila and Bacteroides thetaiotaomicron that rely on mucin degradation for colonization and growth. Alterations in glycosylation patterns of mucins affect microbial composition and functions, and increase the susceptibility to intestinal inflammation. Genome-wide association studies have linked glycosylation-related genes, such as FUT2, B3GALT5 and GAL3ST2, to inflammatory bowel disease (IBD). However, the precise mechanisms by which glycan changes contribute to IBD pathogenesis remain unclear. Further research is needed to clarify these interactions, which may lead to a novel glycan-based therapeutic approach for IBD, including prebiotic or mucin-targeted treatments.