Structure-function Relationships of Human Milk Oligosaccharides

Human milk contains more than a hundred structurally distinct oligosaccharides. In this review, we provide examples of how the structural characteristics of these human milk oligosaccharides (HMO) determine functionality. Specific α1-2-fucosylated HMO have been shown to serve as antiadhesive antimicrobials to protect the breast-fed infant against infections with Campylobacter jejuni, one of the most common causes of bacterial diarrhea. In contrast, α1-2-fucosylation may abolish the beneficial effects of HMO against Entamoeba histolytica, a protozoan parasite that causes colitis, acute dysentery, or chronic diarrhea. In a different context, HMO need to be both fucosylated and sialylated to reduce selectin-mediated leukocyte rolling, adhesion, and activation, which may protect breast-fed infants from excessive immune responses. In addition, our most recent data show that a single HMO that carries not 1 but 2 sialic acids protects neonatal rats from necrotizing enterocolitis, one of the most common and often fatal intestinal disorders in preterm infants. Oligosaccharides currently added to infant formula are structurally different from the oligosaccharides naturally occurring in human milk. Thus, it appears unlikely that they can mimic some of the structure-specific effects of HMO. Recent advances in glycan synthesis and isolation have increased the availability of certain HMO tri- and tetrasaccharides for in vitro and in vivo preclinical studies. In the end, intervention studies are needed to confirm that the structure-specific effects observed at the laboratory bench translate into benefits for the human infant. Ultimately, breastfeeding remains the number one choice to nourish and nurture our infants.