A Glycomic and Genomic Approach to Characterize the Prebiotic Property of Human Breast Milk

David A. Mills(a*), Riccardo LoCascio(a), David Sela(a), Milady Niñonuevo(b), Robert E. Ward(c), Samara Freeman(c), Carlito B. Lebrilla(b), and J. Bruce German(c)
Departments of Viticulture & Enology(a), Chemistry(b), and Food Science & Technology(c), University of California, Davis, CA

Human milk differs from that of other mammals in the high concentration and diversity of free oligosaccharides. Studies suggest these oligosaccharides are resistant to digestion by mammalian hydrolases during transit through the small intestine and thus should arrive in the lower GI tract relatively intact. Breast-feeding has been associated with an infant fecal flora uniquely dominated by select bifidobacterial species. This has led to the hypothesis that milk oligosaccharides function as specific growth factors for amplification of these species in nursing infants.  We propose that oligosaccharide metabolism in infant-borne bifidobacterial species has evolved to consume the extant oligosaccharide diversity present in human milk.  To explore this, we tested several bifidobacterial species for growth on human milk oligosaccharides as a sole carbon source.  Most species readily grew on milk oligosaccharides however the total achievable biomass varied between strains.  Moreover, glycomic profiling of the spent broth indicated differential consumption of specific oligosaccharides by different strains.  One infant-borne isolate, B. longum biotype infantis UCD272, grew to significantly higher cell densities on milk oligosaccharides than all other strains tested.  Genome sequence of UCD272 has revealed numerous genes involved in catabolism of milk oligosaccharides, providing an underlying genetic rationale for the superior growth of UCD272.  Glycomic profiling of milk oligosaccharide consumption by infant-borne bifidobacteria, combined with a genomic analysis of these strains will provide mechanistic insight into the milk-associated enrichment of bifidobacteria in the infant GI tract.