Core fucosylation of maternal milk -glycans imparts early-life immune tolerance through gut microbiota-dependent regulation in RORγt Treg cells

• Published in: Food & function Vol. 15; no. 8; pp. 414 - 4153
• Main Authors: Li, Yuyuan, Ning, Xixi, Zhao, Zihui, He, Xi, Xue, Qidi, Zhou, Manlin, Li, Wenzhe, Li, Ming
• Format: Journal Article
• Published: 22.04.2024
• ISSN: 2042-6496; 2042-650X
• DOI: 10.1039/d4fo00230j

Milk glycans play key roles in shaping and maintaining a healthy infant gut microbiota. Core fucosylation catalyzed by fucosyltransferase (Fut8) is the major glycosylation pattern on human milk N -glycan, which was crucial for promoting the colonization and dominant growth of Bifidobacterium and Lactobacillus spp. in neonates. However, the influence of core-fucose in breast milk on the establishment of early-life immune tolerance remains poorly characterized. In this study, we found that the deficiency of core-fucose in the milk of maternal mice caused by Fut8 gene heterozygosity (Fut8 +/− ) resulted in poor immune tolerance towards the ovalbumin (OVA) challenge, accompanied by a reduced proportion of intestinal RORγt + Treg cells and the abundance of Lactobacillus spp., especially L. reuteri and L. johnsonii , in their breast-fed neonates. The administration of the L. reuteri and L. johnsonii mixture to neonatal mice compromised the OVA-induced allergy and up-regulated the intestinal RORγt + Treg cell proportions. However, Lactobacillus mixture supplementation did not alleviate allergic responses in RORγt + Treg cell-deficient mice caused by Rorc gene heterozygosity (Rorc +/− ) post OVA challenge, indicating that the intervention effects depend on the RORγt + Treg cells. Interestingly, instead of L. reuteri and L. johnsonii , we found that the relative abundance of another Lactobacillus spp., L. murinus , in the gut of the offspring mice was significantly promoted by intervention, which showed enhancing effects on the proliferation of splenic and intestinal RORγt + Treg cells in in vitro studies. The above results indicate that core fucosylation of breast milk N -glycans is beneficial for the establishment of RORγt + Treg cell mediated early-life immune tolerance through the manipulation of symbiotic bacteria in mice. Core fucosylation i breast milk N -glycans was benificial for the establishmet of RORγt + Treg cells-mediated-early-life immune tolerance through manipulation of symbiotic bacteria in neonates.