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.

Ming Li,Wenzhe Li,Di Mei,Zhongfu Wang,Jia Tao,Jianguo Gu,Jingyu Yan,Wei Huang,Qingjie Fan,Patrice Malard,Jiaorui Zhou,Qiulong Yan,Jieli Yuan,Naoyuki Tanigchi,Yaqiang Bai,Yang Liu,Mariya Ivanova Petrova,Xiaorong Lin

doi:10.1128/mbio.00128-19

Abstract

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 Bifidobacterium spp. and Lactobacillus spp. in their breast-fed infants during lactation. Compared with Fut8+/+ (WT) mouse-fed neonates, the offspring fed by Fut8+/- maternal mice had a distinct gut microbial profile, which was featured by a significant reduction of Lactobacillus spp., Bacteroides spp., and Bifidobacterium spp. and increased abundance of members of the Lachnospiraceae NK4A136 group and Akkermansia spp. Moreover, these offspring mice showed a lower proportion of splenic CD19+ CD69+ B lymphocytes and attenuated humoral immune responses upon ovalbumin (OVA) immunization. In vitro studies demonstrated that the chemically synthesized core-fucosylated oligosaccharides possessed the ability to promote the growth of tested Bifidobacterium and Lactobacillus 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.IMPORTANCE 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.

Highlights

The maternal milk glycobiome is crucial for shaping the gut microbiota of infants
It is not a surprise that the fucosylation of human milk include oligosaccharides (HMOs) is mainly catalyzed by fucosyltransferase 2 (Fut2) and Fut3, while the ␣1,6-fucosylated glycotopes on milk glycoproteins were found to be absent on HMOs [44, 45]: the differences in the gut microbiomes observed in infants fed by the G and A groups of mothers were attributed to the different core fucosylation levels of milk N-glycans
Infants fed by mothers with higher-core-fucosylated milk N-glycans (G group) harbored greater abundance of Bifidobacterium spp. and Lactobacillus spp. and reduced abundance of Clostridiales and Pseudomonas during lactation

Summary

Introduction

The maternal milk glycobiome is crucial for shaping the gut microbiota of infants. 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 addition to providing nutrients and energy for newborns [3], glycans in human milk can inhibit the adhesion of pathogens and promote intestinal colonization and growth of probiotics [4, 5], resulting in a Bifidobacterium and Lactobacillus enriched gut micro-ecosystem in breast-fed infants [6, 7]. Once released from the glycoproteins, these glycans can be considered selective growth substrates for infant-associated gut microbes [18, 19]

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