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Symposium: Innate Immunity and Human Milk

Human-Milk Glycans That Inhibit Pathogen Binding Protect Breast-feeding Infants against Infectious Diarrhea^1,2

Ardythe L. Morrow³, Guillermo M. Ruiz-Palacios^*, Xi Jiang and David S. Newburg^**

Center for Epidemiology and Biostatistics and Division of Infectious Diseases, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH; ^* Departamento de Infectologia, Instituto Nacional de Ciencias Medicas y Nutricion, Mexico, DF; and ^** Program in Glycobiology, Mucosal Immunity Laboratory, Massachusetts General Hospital, Boston, MA

³To whom correspondence should be addressed. E-mail: ardythe.morrow{at}cchmc.org.

Breast-feeding is a highly effective strategy for preventing morbidity and mortality in infancy. The human-milk glycans, which include oligosaccharides in their free and conjugated forms, constitute a major and an innate immunologic mechanism by which human milk protects breast-fed infants against infections. The glycans found in human milk function as soluble receptors that inhibit pathogens from adhering to their target receptors on the mucosal surface of the host gastrointestinal tract. The 1,2-linked fucosylated glycans, which require the secretor gene for expression in human milk, are the dominant glycan structure found in the milk of secretor mothers, who constitute the majority (80%) of mothers worldwide. In vitro and in vivo binding studies have demonstrated that 1,2-linked fucosylated glycans inhibit binding by campylobacter, stable toxin of enterotoxigenic Escherichia coli, and major strains of caliciviruses to their target host cell receptors. Consistent with these findings, recently published epidemiologic data demonstrate that higher relative concentrations of 1,2-linked fucosylated glycans in human milk are associated with protection of breast-fed infants against diarrhea caused by campylobacter, caliciviruses, and stable toxin of enterotoxigenic E. coli, and moderate-to-severe diarrhea of all causes. These novel data open the potential for translational research to develop the human-milk glycans as a new class of antimicrobial agents that prevent infection by acting as pathogen anti-adhesion agents.

KEY WORDS: • oligosaccharide • anti-adhesion agents • innate immunity • receptor analogs • histo-blood groups

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