Core Fucosylation of Maternal Milk N-Glycan Evokes B Cell Activation by Selectively Promoting the l-Fucose Metabolism of Gut Bifidobacterium spp. and Lactobacillus spp

The maternal milk glycobiome is crucial for shaping the gut microbiota of infants. Although high core fucosylation catalyzed by fucosyltransferase 8 (Fut8) is a general feature of human milk glycoproteins, its role in the formation of a healthy microbiota has not been evaluated. In this study, we found that the core-fucosylated N-glycans in milk of Chinese mothers selectively promoted the colonization of specific gut microbial groups, such as spp. and spp. in their breast-fed infants during lactation. Compared with (WT) mouse-fed neonates, the offspring fed by maternal mice had a distinct gut microbial profile, which was featured by a significant reduction of spp., spp., and spp. and increased abundance of members of the NK4A136 group and spp. Moreover, these offspring mice showed a lower proportion of splenic CD19 CD69 B lymphocytes and attenuated humoral immune responses upon ovalbumin (OVA) immunization. studies demonstrated that the chemically synthesized core-fucosylated oligosaccharides possessed the ability to promote the growth of tested and strains in minimal medium. The resulting L-fucose metabolites, lactate and 1,2-propanediol, could promote the activation of B cells via the B cell receptor (BCR)-mediated signaling pathway. This study provides novel evidence for the critical role of maternal milk protein glycosylation in shaping early-life gut microbiota and promoting B cell activation of neonates. The special core-fucosylated oligosaccharides might be promising prebiotics for the personalized nutrition of infants.