Abstract • 2

Enteric disease and associated malnutrition result in approximately 11 million infant deaths each year worldwide. Enteric disease morbidity and mortality rates are much lower in breastfed infants than in those fed artificially. The most widely recognized factor contributing to this phenomenon is secretory antibodies found in human milk. However, evidence is mounting that the glycoconjugates and oligosaccharides of human milk might have a major role in preventing enteric disease. Glycoconjugates are molecules that have conjugated carbohydrate moieties, e.g., glycoproteins, glycolipids, glycoaminoglycans, mucins; milk oligosaccharides have carbohydrate moieties attached to lactose. These milk carbohydrate moieties are synthesized in a manner similar to that used by all cells to synthesize their cell surface glycoconjugates, thus, there are often shared structural motifs. Most pathogens use specific host cell glycoconjugates to adhere to and gain entry into their host target cells. Specific human milk oligosaccharides and glycoconjugates have been shown to inhibit binding of specific pathogens to their host cell surface glycoconjugates receptors, blocking their ability to infect these cells. Detailed mechanistic and structural studies exist on fucosylated oligosaccharides that inhibit the pathogenicity of stable toxin of E. coli and Camphylobacter jejuni, and on a glycoprotein lactadherin, that inhibits rotavirus. Many other examples of such inhibition by milk glycoconjugates now exist; this may be a major mechanism of protection by human milk. Human milk olgosaccharides survive transit through the intestine of the breastfeeding infant implying that they are available where needed to protect breast feeding infants from gastroenteritis. There is pronounced individual variation in the expression of oligosaccharides in human milk, suggesting some heterogeneity in the ability of individual human milks to inhibit specific pathogens. Homologous oligosaccharides are found in the milks of other species. Oral supplementation of human milk oligosaccharides or their homologues may be feasible. Human milk oligosaccharides and glycoconjugates may represent a major mechanism whereby breastfeeding protects infants from enteric and other pathogens; this further supports breastfeeding promotion as an important public health measure. Supported by HD 13021 Shriver Center, Waltham, MA 02452 and Harvard Medical School, Boston, MA