Abstract
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 offspring, 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 findings 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.
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Data availability
Datasets are available from corresponding author upon reasonable request.
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Funding
This study was supported by Natural Science Foundation of Liaoning Province (grant no. JYTJCZR201907).
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LW designed this study. JT, YR and ZP carried out the experiments and data analyses. All authors drafted the manuscript and reviewed the final version.
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Jia Tao declares she has no competing interests. Yan Ran declares she has no competing interests. Zhongmin Pan declares she has no competing interests. Li Wang declares she has no competing interests.
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The protocol was approved by the Ethics Committee of the First Affiliated Hospital of Jinzhou Medical University. Written consents were signed by all patients.
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Tao, J., Ran, Y., Pan, Z. et al. Core fucosylation of maternal milk N-glycan prevents intestinal inflammation by regulating Treg/Th17 balance in infant gut microbiota. Mol. Cell. Toxicol. 18, 47–56 (2022). https://doi.org/10.1007/s13273-021-00168-z
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DOI: https://doi.org/10.1007/s13273-021-00168-z