Milk Glycans and Their Interaction with the Infant-Gut Microbiota

Abstract

Human milk is a unique and complex fluid that provides infant nutrition and delivers an array of bioactive molecules that serve various functions. Glycans, abundant in milk, can be found as free oligosaccharides or as glycoconjugates. Milk glycans are increasingly linked to beneficial outcomes in neonates through protection from pathogens and modulation of the immune system. Indeed, these glycans influence the development of the infant and the infant-gut microbiota. Bifidobacterium species commonly are enriched in breastfed infants and are among a limited group of bacteria that readily consume human milk oligosaccharides (HMOs) and milk glycoconjugates. Given the importance of bifidobacteria in infant health, numerous studies have examined the molecular mechanisms they employ to consume HMOs and milk glycans, thus providing insight into this unique enrichment and shedding light on a range of translational opportunities to benefit at-risk infants.

Keywords: Bifidobacterium; glycans; infant microbiota; milk oligosaccharides.

Figure 1

Relative abundances of acidic, acidic fucosylated, neutral fucosylated, and neutral nonfucosylated oligosaccharides in human, bovine, and porcine milk, as demonstrated by selected glycomics studies (Mudd et al. 2016, Ninonuevo et al. 2006, Tao et al. 2009).

Figure 2

Possible strategies of glycan utilization by Bifidobacterium infantis, Bifidobacterium breve, Bifidobacterium longum, and Bifidobacterium bifidum. (Left) B. infantis: galactosidases, hexosaminidases, α-L-fucosidases (GH29), α-L-fucosidase (GH95), sialidases, and lacto-N-biose (LNB) phosphorylase. Described in select strains of B. infantis: α-N-acetylgalactosaminidase (GH 129) and endo-β-N-acetylglucosaminidase (GH 18/85). B. breve: galactosidases, hexosaminidase, α-L-fucosidase (GH95), sialidase, and LNB phosphorylases. Described in select strains of B. breve: α-L-fucosidase (GH29), α-N-Acetylgalactosaminidase (GH 129), endo-β-N-acetylglucosaminidase (GH 18/85), and endo-α-N-acetylgalactosaminidase (GH101). B. longum: galactosidases, hexosaminidase, and LNB phosphorylases. Described in select strains of B. longum: α-L-fucosidase (GH95), α-L-fucosidase (GH29), lacto-N-biosidase, α-N-acetylgalactosaminidase (GH 129), endo-β-N-acetylglucosaminidase (GH 18/85), and endo-α-N-acetylgalactosaminidase (GH101). (Right) B. bifidum: galactosidases, hexosaminidases, α-L-fucosidase (GH29), α-L-fucosidase (GH95), sialidases, LNB phosphorylases, and lacto-N-biosidase. Described in select strains of B. bifidum: α-N-acetylgalactosaminidase (GH 129) and endo-α-N-acetylgalactosaminidase (GH101). Asterisks indicate that the enzyme has been described in select strains.

Figure 3

(a) Endo-β-N-acetylglucosaminidase (EndoBI-1) cleavage of a representative conjugated N-glycan structure. (b) Bifidobacterium infantis growth on whey, released N-glycans from whey, or deglycosylated whey as the sole carbon source. Released N-glycans did not support growth of Bifidobacterium animalis subsp. lactis (data not shown). Adapted from Karav et al. (2016).