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Tao Jia,Ran Yan,Pan Zhongmin,Wang Li 대한독성 유전단백체 학회 2022 Molecular & cellular toxicology Vol.18 No.1
Background This study elucidated the regulatory roles of milk glycoprotein core fucosylation on the gut microbiota of breast-fed infants. Objectives In order to investigate the effects of core fucosylation of maternal milk N-glycan on the intestinal functions in newborn mice, Fut8 +/+ → Fut8 +/+ and Fut8 ± → Fut8 +/+ models were established. Results The results indicated that the gut microbiota diversity was altered and production of Bifidobacterium and Lactobacillus was reduced in the intestine of Fut8 ± → Fut8 +/+ mice . Furthermore, the levels of SCFAs were decreased in the gut of Fut8 ± → Fut8 +/+ infant. To further investigate the effects of core fucosylation of breast milk N-glycan on the intestinal inflammation in newborns, NEC models were established, and Fut8 +/+ off -springs with experimentally induced NEC were fed with the breast milk of Fut8 +/+ and Fut8 ± maternal mice. Our data revealed that reduced core fucosylation of breast milk N-glycan could be responsible for the intestinal inflammation in NEC off spring, as the production of pro-inflammatory cytokines including IL-1b, IL-6, IL-17A and TNF-a was significantly upregulated in Fut8 ± → Fut8 +/+ NEC group, while the levels of anti-inflammatory cytokine IL-10 were remarkably reduced. Furthermore, Treg/Th17 balance in the intestine was disturbed in Fut8 ± → Fut8 +/+ NEC newborn, suggesting the impaired immune development caused by reduced core fucosylation of breast milk. Conclusion These fi ndings indicated that core fucosylation of maternal milk N-glycan could assist the colonization of gut Lactobacillus and Bifidobacterium and regulate the Treg/Th17 balance, subsequently preventing intestinal inflammation in breast-fed newborns.