Mannooligosaccharides modulate mucin O-glycan–gut microbe interactions and preserve the intestinal barrier in weaned piglets

Abstract Background The intestinal microbiota and mucosal barrier are closely intertwined, with mucin O-glycans playing a key role in maintaining intestinal homeostasis. However, how nutrition regulates mucin O-glycans remains poorly understood. This study investigated the regulatory effects of mannooligosaccharides (MOS) on mucin secretion and O-glycan modification in a weaned piglet model. We evaluated the effects of MOS on intestinal morphology, gut microbiota, mucin secretion, and O-glycosylation profiles in weaned piglets. Results Transcriptome analysis revealed that MOS influenced key KEGG pathways, including mucin O-glycan biosynthesis, through the regulation of genes such as GALNT , GCNT3 , and POFUT1 . Furthermore, MOS increased the proportion of Core 2 structures in mucin and modulated the proportion of long-chain, sulfated and sialylated O-glycans, which may help protect the mucus layer from microbial degradation. Moreover, MOS improved colonic microbiota composition by promoting beneficial Lactobacillus species and suppressing potentially pathogenic Escherichia coli . Conclusion This study highlights the molecular effects of MOS on mucin synthesis and modification, which may help preserve intestinal microbiota balance. These effects are important for maintaining intestinal barrier function in weaned piglets.