MS-Based Glycoprofiling of Human Milk Oliogosaccharides Demonstrate a Strain Specific Consumption by Bifidobacteria of Small Chain Glycans Detected in Early Human Lactation

The molecular basis by which human breast milk supports the development of a protective intestinal microbiome in infants is unknown. After lactose and lipids, human milk oligosaccharides (HMOs) are quantitatively the third largest and most diverse component of breast milk. HMOs are believed to provide a range of benefits to the developing infant including protection against pathogens and prebiotic enrichment of beneficial commensals such as bifidobacteria. Our group has previously developed MS-based methods to differentiate over 200 different HMO structures and to quantify bacterial consumption of individual milk oligosaccharide species. MS-based glycomic profiling of HMO consumption by bifidobacteria has shown that one species, Bifidobacterium longum biovar infantis ATCC 15697, an isolate from the infant gut, preferentially consumes four small mass milk oligosaccharides representing nearly 70% of all HMOs present breast milk.  Additional MS glycoprofiling confirmed that these oligosaccharides are secreted early in lactation and three of the four species are fucosylated.  Other tested bifidobacteria do not grow well on pooled HMOs and minimally consumed only one, non-fucosylated HMO. This differential growth on HMOs can be partially explained by the presence of fucosidase activity in B. infantis ATCC 15697 and absent in the other tested strains. This work suggests that small mass HMOs specifically enrich target bifidobacterial strains in the infant gastrointestinal tract. We propose these oligosaccharides represent a new class of bioactive molecules that co-evolved with cognate bifidobacterial strains to facilitate a protective enrichment in breast-fed newborns.