can such an abundant material of such a costly phenotype be undigestible by the individual for whom it is intended, that is, the infant?

What Are Human Milk Oligosaccharides (HMOs), and What Health Benefit Do They Provide the Infant?

Glycobiology2 is “disastrously, catastrophically complex,” German said. According to German, the number of possible glycans, or oligosaccharides, in a biological system is in the billions, based on the number of ways that sugars (the basic structural units of glycans) and linkages (the bonds between sugars) can be combined. This makes sense given that oligosaccharides on cell surfaces are the basis of a recognition system across all life forms. Carlito Lebrilla developed a methodology for analyzing glycan complexity in human milk, based on innovative separation technologies and very high-efficiency, high-accuracy mass spectrometry (Ninonuevo et al., 2006). His research team has constructed an annotated database of the nearly 200 highly variable structural compositions of HMO (Wu et al., 2010, 2011).

David Mills was among the first to address the question, What do HMOs do? He hypothesized that HMOs serve as a food source for the infant microbiome. However when he and his colleagues tested bacterial growth on HMO as a sole food source, none but Bifidobacterium infantis grew (Ward et al., 2007). “Perhaps we shouldn’t be surprised,” German said, given that B. infantis is a dominant member of the breast-fed-infant microbiome. Moreover, Mills and his group have discovered that only very specific strains of B. infantis grow on HMO medium. Even bacteria that grow very well on a variety of other sugar media are unable to grow on HMO medium (Marcobal et al., 2010; Ward et al., 2006). (The only other genus that appears to be able to grow on HMO medium is Bacteroides. However, as both German and, later during the question-and-answer period, Mills explained, B. infantis readily outcompetes Bacteroides when the two are grown together.) “What we are discovering about this remarkable interaction between milk oligosaccharides and this particular bacterium is remarkable,” German said. “Mothers are literally recruiting another life form to babysit their babies and using the oligosaccharides to direct the microbiome.”

How does the system work? For example, if oligosaccharides are serving as a food source for B. infantis, which oligosaccharides are being consumed? Mills and his group have discovered that unlike other bifidobacteria, B. infantis selectively cleaves and eliminates sialic acid–containing


2 Glycobiology is the study of the structure, biosynthesis, and biology of glycans, also called oligosaccharides (i.e., sugar chains).

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