Human Milk Oligosaccharides (HMO) are complex carbohydrates that are highly abundant in human milk, but not in infant formula. Oligosaccharide concentrations in human milk vary with the stage of lactation, and both amount and composition are highly variable between different women. Colostrum, the thick, yellowish fluid secreted by the mammary gland a few days before and after parturition, contains as much as 20-30 g HMO. As milk production matures, HMO concentrations decline to 5-15 g/L, which still exceeds the concentration of total milk protein. The milk of mothers delivering preterm infants has higher HMO concentrations than term milk.
HMO are composed of the five monosaccharides glucose (Glc, blue circle), galactose (Gal, yellow circle), N-acetylglucosamine (GlcNAc, blue square), fucose (Fuc, red triangle) and sialic acid (Sia, pruple diamond), with N-acetylneuraminic acid (Neu5Ac) as the predominant if not only form of Sia. HMO biosynthesis appears to follow a basic blueprint as shown to the right.
All HMO contain lactose at their reducing end, which can be elongated by the addition of beta1-3- or beta1-6-linked lacto-N-biose (Gal beta1-3GlcNAc-, type 1 chain) or N-acetyllactosamine (Gal beta1-4GlcNAc-, type 2 chain). Elongation with lacto-N-biose appears to terminate the chain, whereas N-acetyllactosamine can be further extended by the addition of one of the two disaccharides. A beta1-6 linkage between two disaccharide units introduces chain branching. Branched structures are designated as iso-HMO; linear structures without branches as para-HMO. Lactose or the elongated oligosaccharide chain can be fucosylated in alpha1-2, alpha1-3 or alpha1-4 linkage and/or sialylated in alpha2-3 or alpha2-6 linkage. Some HMO occur in several isomeric forms, e.g. lacto-N-fucopentaose (LNFP) or sialyllacto-N-tetraose (LST).