Consumption of human milk glycoconjugates by infant-associated bifidobacteria: mechanisms and implications

Abstract

Human milk is a rich source of nutrients and energy, shaped by mammalian evolution to provide all the nutritive requirements of the newborn. In addition, several molecules in breast milk act as bioactive agents, playing an important role in infant protection and guiding a proper development. While major breast milk nutrients such as lactose, lipids and proteins are readily digested and consumed by the infant, other molecules, such as human milk oligosaccharides and glycosylated proteins and lipids, can escape intestinal digestion and transit through the gastrointestinal tract. In this environment, these molecules guide the composition of the developing infant intestinal microbiota by preventing the colonization of enteric pathogens and providing carbon and nitrogen sources for other colonic commensals. Only a few bacteria, in particular Bifidobacterium species, can gain access to the energetic content of milk as it is displayed in the colon, probably contributing to their predominance in the intestinal microbiota in the first year of life. Bifidobacteria deploy exquisite molecular mechanisms to utilize human milk oligosaccharides, and recent evidence indicates that their activities also target other human milk glycoconjugates. Here, we review advances in our understanding of how these microbes have been shaped by breast milk components and the strategies associated with their consumption of milk glycoconjugates.

Figures

Fig. 1.

Structural diversity of glycans in human milk and corresponding glycosyl hydrolases in infant-gut associated bifidobacteria. Legends at the bottom left indicate monosaccharide composition and the corresponding potential glycolytic enzymes in bifidobacteria acting at specific linkages. A: illustrative structure of HMO; B: three different cores found in human O-linked glycans; C: glycolipids, the structure of ganglioside GD3 is shown; D: a complex N-glycan.

Fig. 2.

Clusters of genes in B. infantis ATCC 15697 with assigned or putative functions in the utilization of milk glycans. Numbers above the arrows correspond to the respective locus tags (Blon_xxxx). Genes are not drawn to scale, and the genome circle was adapted from Sela et al. (2008). SBPs from ABC transporters with affinities for HMO and expressed during growth on these substrates were identified by Garrido et al. (2011). An α-sialidase and two α-fucosidases were characterized by Sela et al. (2011, . Two β-galactosidases and three β-hexosaminidases active on different linkages in representative HMO are also included (Garrido et al., 2012c; Yoshida et al., 2012). Finally, potential gene clusters for N-linked and O-linked glycan utilization (*) are depicted (Garrido et al., 2012b; Kiyohara et al., 2012).