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Updated: Mar 16, 2026

Profiling of Permethylated Mucin O-glycans Using Matrix-assisted Laser Desorption/Ionization Time-of-flight Mass Spectrometry
Published on: June 20, 2025
Fine structural features of polysaccharides and gut microbiota Co-regulate mucin O-glycosylation: Mechanisms and
Tong Zhao1, Bo Zhang1, Xuansheng Hu1
1Shangluo University, School of Biomedical and Food Engineering, Shangluo, 726000, China.
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.
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