Histo-blood group antigen and human milk oligosaccharides: genetic polymorphism and risk of infectious diseases.

ABH and Lewis antigens are carbohydrates present on gut epithelial cells. These antigens provide diversity within the human population. Their biosynthesis largely is controlled by the enzyme products of alleles at the ABO, FUT2 and FUT3 loci. We have shown that Norwalk virus (NV) uses structures based on H type 1 as its primary receptor. Norwalk virus is the prototype of human caliciviruses, which collectively are responsible for the majority of gastroenteritis outbreaks in people of all ages. Individuals with two mutated FUT2 alleles, and therefore devoid of H type 1 epitopes on their gut epithelial cells, are called nonsecretors and are resistant to infection by NV. This genetically controlled mechanism of resistance to NV also might be important in the protection of infants by human milk, yet in an inverse manner since, unlike milk from secretors, the milk from nonsecretor mothers does not inhibit attachment of recombinant NV particles to their primary receptor. This suggests that breastfeeding by a secretor mother should protect a secretor child from NV infection, whereas breastfeeding by a nonsecretor mother should not.