Fine structural features of polysaccharides and gut microbiota Co-regulate mucin O-glycosylation: Mechanisms and advances

Abstract

Mucin O-glycosylation is a key mechanism maintaining intestinal homeostasis and involving complex crosstalk between mucin glycan structures and microbial metabolism. Polysaccharides, as primary carbon sources for gut microbes, exert structure-dependent effects—through monosaccharide composition, glycosidic linkages, molecular weight, branching patterns, and chemical modifications—on microbial colonization and metabolism. Microbial metabolites, including short-chain fatty acids (SCFAs) and bile acids, further regulate host glycosyltransferase expression, thereby remodeling mucin O-glycans. Meanwhile, bacterial glycosidases (e.g., fucosidases and sialidases) dynamically remodel Core 1/Core 2 structures and terminal decorations, altering mucus properties and microbial adhesion. This review summarizes how polysaccharide fine structures influence the microbial community composition and mucin O-glycosylation, emphasizing the “SCFAs–G protein-coupled receptor (GPCR) / Histone deacetylase (HDAC)” axis in glycosyltransferase regulation. Analyses of disease models reveal that reduced sulfation/sialylation and core-structure decomplexification are hallmarks of pathological mucin remodeling, with distinct mechanisms across disease contexts. For example, in inflammatory bowel disease (IBD), H₂S-induced disruption of mucin disulfide bonds synergizes with microbial enzymes, whereas in allergic models, SCFA–Treg signaling modulates glycosylation indirectly. Finally, we highlight structural design of polysaccharides, microbial modulation, and enzyme inhibition as potential strategies for therapeutic intervention and propose glycan-targeted prebiotics for precise regulation of mucosal barrier function.