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Influencing Factors on Human Milk Oligosaccharides in Breast Milk

Breast milk is the natural and most perfect food for babies, providing energy and nutrients adapted to the changing needs of the developing baby during exclusive breastfeeding in the first 4 to 6 months of life.(1, 2) Hence, breast milk is a dynamic fluid with changes in its composition occurring throughout lactation.(2)

Scientists could also show that human milk oligosaccharides (HMOs) change over the course of lactation.(3-5) The levels of total HMOs are higher during the early stages of lactation (mean levels of 20-25 g/L in the colostrum) and decrease over time (mean levels of 10-15 g/L in mature milk).(5-7) Most individual HMOs, such as 2′FL (2′fucosyllactose) and LNnT (lacto-N-neotetraose) follow the same pattern.(8, 9)

Moreover, the amount and composition of HMOs vary considerably among women, which is largely related to the mothers’ genes.(3, 5, 10) Research has shown that HMOs in breast milk mirror the mothers’ blood group characteristics, especially the presence or absence of secretor and/or Lewis blood group genes.(3, 5, 6, 10) The secretor gene accounts for the most extreme variations in HMOs among women.(6) It is responsible for producing the FUT2 (fucosyltransferase 2) enzyme, which is necessary for creating 2′FL and other 1,2 fucosylated HMOs.(3, 5, 6, 10) Milk of secretor women, therefore, contains 1,2 fucosylated HMOs in abundance, especially 2′FL, while the milk of non-secretor women does not contain, or contain in minimal amounts, 2′FL and other 1,2 fucosylated HMOs.(4, 9, 10) As a further consequence, the amount of total HMOs in milk of secretor mothers is about 35% to 45% higher than in milk of non-secretor mothers.(10)

Interestingly, breast milk with high levels of 2′FL also contains higher levels of LNnT, but lower levels of LNT than in milk of non-secretor women, indicating that these non-fucosylated HMOs are ‘co-regulated’ with the FUT2 depending on 2′FL levels.(9) In contrast, the sialylated HMOs do not depend on the secretor status.(10)

Worldwide, the majority of mothers are secretors; about 80% of the European and American are secretors, while this ratio can be lower in some regions of Africa (60%-85%) and Asia (46%-80%).(6, 8, 11, 12)
Other factors may also drive HMO content and profiles in breast milk, as indicated by a recent study showing that HMOs vary geographically, even when the known mothers’ blood group characteristics were considered.(11)
Furthermore, a recent study found no differences in total HMO content between breast milk from mothers who delivered at term and preterm (10), and did not confirm previous observations (12).
In conclusion, HMO content and profiles in breast milk are largely influenced by the course of lactation and mothers’ secretor status.(5, 6, 9, 10)

Professor Clemens Kunz, University Giessen, Germany

 The potential influence of the mothers’ secretor or non-secretor status on the infants’ health is of great interest. For example, observational studies indicate that infants who receive secretor milk seem to be     better protected against Campylobacter-induced diarrhoea but may be more susceptible to certain genotypes of Norovirus. Hence, there is a strong indication that fucosylated HMOs play an important role in   infant healthy development. 2′FL, which is safe to be added to infant formula, is currently investigated for its potential preventive effect on gastrointestinal diseases.
 Another intriguing aspect is the question whether it matters if an infant receives ‘non-secretor milk’ without 1,2-fucosylated HMOs; and, is it a potential disadvantage if the infant itself is a ‘secretor’? These   questions relate to our own observations showing that in the urine of those infants 1,2 fucosylated oligosaccharides can be often detected. Hence, themother’s sector status may not matter, provided the infant   is a secretor.

 These are amazing questions that can only be addressed by metabolic studies, considering infants’ own secretor status.

References

1. Agostoni C, Braegger C, Decsi T, Kolacek S, Koletzko B, Michaelsen KF, et al. Breast-feeding: a commentary by the ESPGHAN Committee on Nutrition. J Pediatr Gastroenterol Nutr. 2009;49(1):112-25.
2. Lonnerdal B, Hernell O. An opinion on "staging" of infant formula: a developmental perspective on infant feeding. J Pediatr Gastroenterol Nutr. 2016;62(1):9-21.
3. Kunz C, Rudloff S, Baier W, Klein N, Strobel S. Oligosaccharides in human milk: structural, functional, and metabolic aspects. Annu Rev Nutr. 2000;20:699-722.
4. Thurl S, Munzert M, Henker J, Boehm G, Muller-Werner B, Jelinek J, et al. Variation of human milk oligosaccharides in relation to milk groups and lactational periods. Br J Nutr. 2010;104(9):1261-71.
5. Bode L. Human milk oligosaccharides: every baby needs a sugar mama. Glycobiology. 2012;22(9):1147-62.
6. Vandenplas Y, Berger B, Carnielli VP, Ksiazyk J, Lagstrom H, Sanchez Luna M, et al. Human milk oligosaccharides: 2'-fucosyllactose (2'-FL) and lacto-N-neotetraose (LNnT) in infant formula. Nutrients. 2018;10(9):1161.
7. Zivkovic AM, German JB, Lebrilla CB, Mills DA. Human milk glycobiome and its impact on the infant gastrointestinal microbiota. Proc Natl Acad Sci USA. 2011;108 (Suppl 1):4653-8.
8. Austin S, De Castro CA, Benet T, Hou Y, Sun H, Thakkar SK, et al. Temporal change of the content of 10 oligosaccharides in the milk of Chinese urban mothers. Nutrients. 2016;8(6).
9. Sprenger N, Lee LY, De Castro CA, Steenhout P, Thakkar SK. Longitudinal change of selected human milk oligosaccharides and association to infants' growth, an observatory, single center, longitudinal cohort study. PLoS        One. 2017;12(2):e0171814.
10. Kunz C, Meyer C, Collado MC, Geiger L, Garcia-Mantrana I, Bertua-Rios B, et al. Influence of gestational age, secretor, and Lewis blood group status on the oligosaccharide content of human milk. J Pediatr Gastroenterol      Nutr. 2017;64(5):789-98.
11. McGuire MK, Meehan CL, McGuire MA, Williams JE, Foster J, Sellen DW, et al. What's normal? Oligosaccharide concentrations and profiles in milk produced by healthy women vary geographically. Am J Clin Nutr. 2017;105(5):1086-100.
12. De Leoz ML, Gaerlan SC, Strum JS, Dimapasoc LM, Mirmiran M, Tancredi DJ, et al. Lacto-N-tetraose, fucosylation, and secretor status are highly variable in human milk oligosaccharides from women delivering preterm. J Proteome Res. 2012;11(9):4662-72.
 

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