Human Milk Oligosaccharides: Health Benefits, Potential Applications in Infant Formulas and Pharmacology
The health and care of an infant in their first six months of life are critical as they undergo rapid development. It is important that infants are provided with adequate nutrition. Human breast milk is sometimes referred to as “living tissue” as it contains the optimum amount of nutrients for infants and contains immunoglobulins, hormones, oligosaccharides and other bioactive compounds (1, 2). Human milk oligosaccharides (HMOs) are multifunctional glycans found in human milk. The concentration of HMOs in breast milk varies between women and changes during lactation stages (4). The highest concentration of HMOs is found in colostrum, beginning at around 20-23 g/L and dropping to 12-14 g/L (6). HMO structure is based on lactose molecules and five monosaccharides make up the structure of HMOs: glucose, galactose, N-ethylglucosamine, fucose, and sialic acid (3). About 1% of HMOs are absorbed in circulation when ingested, the remainder is metabolised by gut microbes or excreted (5).
Galactooligosaccharides (GOSs) and fructooligosaccharides (FOSs) are compounds that have been developed for infant formulas that mimic the nutritional benefits and composition of breast milk. GOS contains lactose at the reducing end and extend to six galactose residues and FOS consists of linear polymers of fructose (7). Although GOSs and FOSs are different and structurally simpler than HMOs, studies have shown that they help to reduce the incidence of infections in infants.
HMOs have antiviral and antibacterial properties. HMOs are able to prevent pathogen adhesion to epithelial cells as they resemble glycan structures, which the pathogens bind to instead of epithelial cells. Studies have shown that HMOs can modify the glycan content on the surface of epithelial cells and receptor site to prevent pathogen binding (4,5). 2’FL attenuates C. jejuni invasion by 80%, which is believed to reduce diarrheal episodes associated with the bacteria. LNnT has been shown to decrease the amount of S. pneumonia in the lungs when studied in animal models (4). The anti-adhesive properties of HMOs possibly explain why breastfed infants have a lower infection rate of E. histolytica, a parasitic disease that causes 100,000 annually, than non-breastfed infants (11).
Studies have shown that infants given infant formulas supplemented with 2’-fucosyllactose (2’FL) and lacto-N-neotetraose (LNnT), two HMOs, have microflora more similar to breastfed infants than those fed formulas without milk (8,9).
Intestinal health and microbiota composition is improved by the presence of HMOs in infant diets. In breastfed infants, bifidobacteria are the dominant colonising bacteria, this occurs as the result of consumption of bifidogenic agents, such as oligosaccharides. HMOs are able to indirectly increase short-chain fatty acid (SCFA) production, which is a source of energy for cells of the intestinal lining. HMOs meet all of the criteria for a prebiotic, which are used to increase the amount of bifidobacteria in the large intestine to promote gastrointestinal and overall health. SCFAs are not only important for intestinal health but are also involved in the activation and differentiation of immune cells (10,11). HMOs provide protection against viral pathogens by stimulating the immune response and promoting the mature of the immune system and epithelial cells (12,13). The antiviral captivity of HMOs stems from their structural similarity to cell surface carbohydrates. Fucosylated and HMOs catch viruses and block lectin receptors on the surface of epithelia cells. For example, the HMO 2-fucosyllactose (2’FL) trisaccharide is able to block norovirus binding (14).
Studies on animal models have shown that HMOs consisting of 3’SL, 6’SL, 2’FL and GOSs (sialylated and fucosylated oligosaccharides) reduced the infectivity of human rotaviruses (5). Rotaviruses-induced gastroenteritis occurs less in breastfed infants (15). HMOs LNnT and 6’SL have been shown to reduce the influence of viral load and 2’FL has been shown to reduce RSV viral load, leading to the conclusion that HMOs increase innate immunity and affect immune cell differentiation (16). There is evidence to support that exclusive breastfeeding for the first six months of life reduces the incidence of asthma, allergies, inflammatory bowel disease, type 1 diabetes, celiac disease and leukaemia. Breastfed infants also have a 6-10x lower risk of developing necrotising enterocolitis (NEC), which kills about ¼ of the infants diagnosed (17).
HMOs, GOSs and FOSs have been found to support bone health by increasing bone mineralisation and, density and structure as well as increasing the absorption of Ca, P and Mg (18). Ongoing research continues to identify the possible uses of HMOs as a dietary supplement, an addition to infant formulas, as a therapeutic treatment for allergies and much more.
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