Human milk oligosaccharides (HMO) are biologically active molecules in human milk that provide a source of energy for the microflora within the intestine of the infant during breast feeding. In addition, they also provide direct stimulation of the immune system and may prevent pathogenic bacteria from adhering to the epithelial surface of the gut. Structurally, HMO consist of a diverse group of oligosaccharides that display a wide array of structural variants. Generally, they consist of a lactose molecule linked by β(1-3) or β(1-6) bonds to lactosamine (N-acetylglucosamine bonded to galactose) units often with a branched structure. Additional fructose and sialic acid units are bonded to the terminal positions by α(1-2), α(1-3), or α(1-4); and α(2-3) and α(2-6) linkages, respectively (here). It is likely that the complex structures and variability of molecules produces a synergistic effect that enhances protection of the infant from pathogens and immune disorders.
Human milk oligosaccharides are prebiotic substances because they pass through the upper gut undigested and are then used as a source of energy by colonic bacteria. Prebiotic substances such as HMOs tend to increase the quantity of saccharolytic bacteria such as bifidobacteria and lactobacilli, and this growth causes an acidic environment via short chain fatty acid production, that is detrimental to the growth of potentially harmful bacteria such as clostridia, eubacteria, and enteroocci. Evidence suggests that a healthy breastfed infant gut contains around 90% bifidobacteria and lactobacilli, and it is under these conditions that the development of a healthy immune system proceeds. In contrast, formula fed infants fend to have microbiota that resembles that of adults. Lack of a dominant bifidobacteria and lactobacilli environment in infants is thought to lead to the development of allergy and other immune disorders by the age of around 2 years.
There is evidence that a small amount of absorbance of HMOs occurs in the intestine, and this is required for their direct immune stimulatory effects. Human milk oligosaccharides that are absorbed have an immune modulatory effect and are thought to be reduce allergy, inhibit immune cell recruitment, reduce immune cell adhesion to epithelial cells, and may also have direct effect against pathogenic bacteria and viruses. The intestinal mucosa has a large surface area that is covered by glycans such as glycoproteins, glycolipids and mucins. Pathogenic bacteria and viruses can bind to specific glycans with sialylated and fructosylated oligosaccharides being the principle target. Because these sialylated and fructosylated oligosaccharide are present in HMOs on homologous structural units, it is thought that they can prevent the bacterial and viruses adhering to epithelial cells in the gut by acting as structural analogues.
While HMO are known to be beneficial to the immune system of human infants through breastfeeding, they are not commercially available. However, FOS, GOS and other plant based non-digestible polysaccharides such as lactulose provide a commercially available alternative prebiotic, and research on adults have found similar immune modulatory effects. Plant based oligosaccharides tend to be less complex than HMOs, with linear chains absent the branching lactosamine and without the terminal fructose or sialic acid residues (here). Bovine milk also contains oligosaccharides (bovine milk oligosaccharides; BMO), which tend to be a mixture of simple and complex structures. Bovine milk oligosaccharides are only present in mature milk at very low amounts, although they are present in much higher amounts in colostrum. Because of their relative scarcity in the human diet, there is little research investigating BMOs, and so it is at present unclear as to their effects on human health.
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