Human milk oligosaccharide

Human milk oligosaccharides (HMO, also known as human milk glycans) are sugar molecules, that are part of the oligosaccharides group and which can be found in high concentrations exclusively in human breast milk.[1]

Occurrence

Human milk oligosaccharides form the third most abundant solid component (dissolved or emulsified or suspended in water) of human milk after lactose and fat.[2] HMOs are present in a concentration of 0.35–0.88 ounces (9.9–24.9 g)/ L. Approximately 200 structurally different human milk oligosaccharides are known. The composition of human milk oligosaccharides in breast milk is individual to each mother and varies over the period of lactation. The dominant oligosaccharide in 80% of all women is 2'-fucosyllactose, which is present in human breast milk at a concentration of approximately 2.5 g/ L.[3] Other oligosacchardies include lacto-N-tetraose, lacto-N-neotetraose, and lacto-N-fucopentaose.[4]

Characteristics

In contrast to the other components of breast milk that are absorbed by the infant through breastfeeding, HMOs are indigestible for the newborn child. However, they have a prebiotic effect and serve as food for intestinal bacteria, especially bifidobacteria.[5] The dominance of these intestinal bacteria in the gut reduces the colonization with pathogenic bacteria (probiosis) and thereby ensures a healthy intestinal flora (intestinal microbiome) and a reduced risk of dangerous intestinal infections.

Recent studies also suggest that HMOs significantly lower the risk of viral and bacterial infections and thus diminish the chance to get diarrhoea and respiratory diseases.

This protective function of the HMOs is activated when in contact with specific pathogens, such as certain bacteria or viruses. These have the ability to bind themselves to the glycan receptors (receptors for long chains of connected sugar molecules on the surface of human cells) located on the surface of the intestinal cells and can thereby infect the cells of the intestinal mucosa. Researchers have discovered that HMOs mimic these glycan receptors so the pathogens bind themselves to the HMOs rather than the intestinal cells. This reduces the risk of an infection with a pathogen.[1][3] In addition to this, HMOs seem to influence the reaction of specific cells of the immune system in a way that reduces inflammatory responses.[1][6] It is also suspected that HMOs reduce the risk of premature infants becoming infected with the potentially life-threatening disease necrotizing enterocolitis (NEC).[1]

Some of the metabolites directly affect the nervous system or the brain and can sometimes influence the development and behavior of children in the long term. There are studies that indicate certain HMOs supply the child with sialic acid residues. Sialic acid is an essential nutrient for the development of the child’s brain and mental abilities.[1][6]

HMOs are used as supplements in baby food to ensure a provision of babies that are not being breastfed with this important component of the human milk.[7]

Evolution

In experiments designed to test the suitability of HMOs as a prebiotic source of carbon for intestinal bacteria it was discovered that they are highly selective for a commensal bacteria known as Bifidobacteria longum biovar infantis. The presence of genes unique to B. infantis, including co-regulated glycosidases, and its efficiency at using HMOs as a carbon source may imply a co-evolution of HMOs and the genetic capability of select bacteria to utilize them.[8]

Enzymatic synthesis and large-scale production

Enzymatic synthesis of HMOs through transgalactosylation is an efficient way for the large-scale production. Various donors, including p-nitrophenyl β-galactopyranoside, uridine diphosphate galactose and lactose, can be used in transgalactosylation. In particular, lactose may act as either a donor or an acceptor in a variety of enzymatic reactions and is available in large quantities from the whey produced as a co-processing product from cheese production. There is a lack of published data, however, describing the large-scale production of such galactooligosaccharides.[9]

References

1. Bode, L. (2012). "Human milk oligosaccharides: every baby needs a sugar mama.". Glycobiology. 22 (9): 1147–1162. doi:10.1093/glycob/cws074. PMC 3406618. PMID 22513036.
2. Chen, X. (2015). "Human Milk Oligosaccharides (HMOS): Structure, Function, and Enzyme-Catalyzed Synthesis.". Advances in Carbohydrate Chemistry and Biochemistry. 72: 113–190. doi:10.1016/bs.accb.2015.08.002. PMID 26613816.
3. Katja Parschat, Bettina Gutiérrez (November 2016), "Fermentativ erzeugte humane Milch-Oligosaccharide wirken präbiotisch.", Dei – die Ernährungsindustrie (in German), p. 38
4. Miesfeld, Roger L. (July 2017). Biochemistry. McEvoy, Megan M. (First ed.). New York, NY. ISBN 978-0-393-61402-2. OCLC 952277065.
5. Doare, K. Le; Holder, B.; Bassett, A.; Pannaraj, P. S. (2018). "Mother's Milk: A Purposeful Contribution to the Development of the Infant Microbiota and Immunity.". Frontiers in Immunology. 9: 361. doi:10.3389/fimmu.2018.00361. PMC 5863526. PMID 29599768.
6. Newburg, D. S.; He, Y. (2015). "Neonatal Gut Microbiota and Human Milk Glycans Cooperate to Attenuate Infection and Inflammation.". Clinical Obstetrics and Gynecology. 58 (4): 814–826. doi:10.1097/GRF.0000000000000156. PMID 26457857.
7. Ralph Ammann (May 2017), "Achieving the impossible", European Dairy Magazine (in German), pp. 30 f
8. German, JB; Lebrilla, CB; Mills, DA (18 Apr 2012). Human milk oligosaccharides: evolution, structures and bioselectivity as substrates for intestinal bacteria. Nestle Nutr Workshop Ser Pediatr Program. Nestlé Nutrition Workshop Series: Pediatric Program. 62. pp. 205–22. doi:10.1159/000146322. ISBN 978-3-8055-8553-8. PMC 2861563. PMID 18626202.
9. Karimi Alavijeh, M.; Meyer, A.S.; Gras, S.L.; Kentish, S.E. (February 2020). "Simulation and economic assessment of large-scale enzymatic N-acetyllactosamine manufacture". Biochemical Engineering Journal. 154: 107459. doi:10.1016/j.bej.2019.107459.