Human milk contains a large fraction of unconjugated glycans. This heterogeneous mixture of Human Milk Oligosaccharides (HMO) acts as antiadhesive mimics of epithelial O-glycans lowering the risk of viral, bacterial and protozoan infections; promotes the formation of a healthy intestinal microbiome in infants; and lowers the chance of necrotizing enterocolitis. High heterogeneity makes it difficult to examine properties of individual HMOs. Chemical and enzymatic synthesis has focused exclusively on simple symmetrical structures, despite human milk containing highly complex asymmetrical multiantennary architectures.
To address this problem, we developed a chemo-enzymatic strategy for the controlled synthesis of asymmetrically branched HMOs. Individual HMOs are printed on a glycan microarray to establish structure-activity relationships with human and viral lectins. Effects on the gut microbiome composition have been investigated in vitro with an intestinal microbiota screening platform.
