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

mBio. 2019 Apr 2;10(2):e00128-19. 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.

Keywords: B cells; Bifidobacterium; Lactobacillus; core fucosylation; infants; milk N-glycan.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / immunology*
  • Bifidobacterium / metabolism*
  • China
  • Female
  • Fucose / metabolism*
  • Gastrointestinal Tract / immunology*
  • Gastrointestinal Tract / microbiology
  • Humans
  • Infant
  • Lactobacillus / metabolism*
  • Lymphocyte Activation
  • Mice
  • Milk, Human / chemistry*
  • Polysaccharides / chemistry
  • Polysaccharides / metabolism*

Substances

  • Polysaccharides
  • Fucose