Potential Benefits of adding Human Milk Oligosaccharides to Infant Formulae
Human breast milk is nature’s most perfect source of nutrition, providing everything a baby needs to grow and develop healthily. Moreover, breast milk supports the development of a healthy gut microbiota and provides many short-term and long-term health benefits for babies.
Surprisingly, in the mix of many different elements of breast milk, the third most common solid component – human milk oligosaccharides (HMOs) – has virtually no nutritive benefits. HMOs are synthesised by the mammary gland and about 200 structures have been identified, to date. HMOs are unique to human milk, they are either absent or in very low amounts in cow’s milk or any milk from farmed animals.Growing evidence suggests that HMOs provide unique benefits to babies, including protection against infection at a time when they are most vulnerable.Hence, the difference in oligosaccharide content among breast milk and
Due to breakthrough advances in biotechnology, 2′-fucosyllactose (2′FL) and lacto-N-neotetraose (LNnT) – 2 of the most abundant and researched HMOs – can now be produced structurally identical to those in breast milk.More importantly, these HMOs are recognised as safe to be added to infant formulae.
A first, randomised, controlled clinical study showed that infants receiving infant formula with 2′FL and LNnT had higher levels of beneficial bifidobacteria in the gut closer to that of breastfed infants and were less susceptible to parent-reported respiratory infections and bronchitis.This resulted in a less frequent use of antipyretic and antibiotic medication in babies, which was also noticed by the parents. Another randomised, controlled clinical study in infants reported that 2′FL, when added to an infant formula, reached systemic circulation beyond the gut and helped lower several inflammatory cytokines to be more like levels in breastfed infants.
Professor Hania Szajewska, Department of Paediatrics of the Medical University of Warsaw, Poland
The administration of currently evaluated HMO-supplemented formulae (with 2′FL and LNnT) to healthy infants does not raise safety concerns with regard to growth and adverse effects. Some favourable clinical effects are possible. Among them, the reduced use of antibiotics is noteworthy. Infants’ exposure to antibiotics is considered to be one of the strongest modulating factors of microbiota in early life, leading to an altered gut microbiota composition and/or activity (dysbiosis). Numerous studies suggest that such changes in the gut microbiota may contribute to the pathogenesis of various diseases, including allergy and obesity. Any intervention that would reduce antibiotic administration is worth considering. However, further high-quality randomised clinical trials are needed to document this, and other clinical effects of infant formulae supplemented with HMOs. These trials should assess outcomes validated by experts in the field of infant nutrition, over a longer period of time. Future research should also examine the optimal composition and dosage for HMO interventions and consider effectiveness in different settings/populations. Stay tuned for future publications.
1. Agostoni C, Braegger C, Decsi T, et al. Breast-feeding: a commentary by the ESPGHAN Committee on Nutrition. J Pediatr Gastroenterol Nutr. 2009;49(1):112-25.
2. Breastfeeding So. Breastfeeding and the use of human milk. Pediatrics. 2012;129(3):e827-41.
3. WHO WHO. Infant and young child feeding. Model chapter for textbooks for medical students and allied health professionals. 2009.
4. Collado MC, Cernada M, Bauerl C, Vento M, Perez-Martinez G. Microbial ecology and host-microbiota interactions during early life stages. Gut Microbes. 2012;3(4):352-65.
5. Victora CG, Bahl R, Barros AJ, et al. Breastfeeding in the 21st century: epidemiology, mechanisms, and lifelong effect. Lancet. 2016;387(10017):475-90.
6. Horta BL, Victora CG. Short-term effects of breastfeeding: a systematic review on the benefits of breastfeeding on diarrhoea and pneumonia mortality. 2013; [cited 2019, October 30th]. Available from: https://apps.who.int/iris/bitstream/handle/10665/95585/9789241506120_eng.pdf;
7. Bachrach VR, Schwarz E, Bachrach LR. Breastfeeding and the risk of hospitalization for respiratory disease in infancy: a meta-analysis. Arch Pediatr Adolesc Med. 2003;157(3):237-43.
8. Bode L. Human milk oligosaccharides: every baby needs a sugar mama. Glycobiology. 2012;22(9):1147-62.
9. 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):4653-58.
10. Ruhaak LR, Lebrilla CB. Advances in analysis of human milk oligosaccharides. Adv Nutr. 2012;3(3):406S-14S.
11. Vandenplas Y, Berger B, Carnielli VP, et al. Human milk oligosaccharides: 2'-fucosyllactose (2'-FL) and lacto-N-neotetraose (LNnT) in infant formula. Nutrients. 2018;10(9):1161.
12. Donovan SM, Comstock SS. Human milk oligosaccharides influence neonatal mucosal and systemic immunity. Ann Nutr Metab. 2016;69 (Suppl 2):42-51.
13. Morrow AL, Ruiz-Palacios GM, Altaye M, et al. Human milk oligosaccharides are associated with protection against diarrhea in breast-fed infants. J Pediatr. 2004;145(3):297-303.
14. Stepans MB, Wilhelm SL, Hertzog M, et al. Early consumption of human milk oligosaccharides is inversely related to subsequent risk of respiratory and enteric disease in infants. Breastfeed Med. 2006;1(4):207-15.
15. Samuel TM, Binia A, de Castro CA, et al. Impact of maternal characteristics on human milk oligosaccharide composition over the first 4 months of lactation in a cohort of healthy European mothers. Sci Rep. 2019;9(1):11767.
16. Agostoni C, Berni Canani R, Fairweather-Tait S, et al. Safety of lacto-N-neotetraose as a novel food ingredient pursuant to Regulation (EC) No 258/97. EFSA Journal 2015;13(7).
17. Agostoni C, Berni Canani R, Fairweather-Tait S, et al. Safety of 2'-O-fucosyllactose as a novel food ingredient pursuant to Regulation (EC) No 258/97. EFSA Journal 2015;13(7).
18. FDA UFaDA. Agency response letter GRAS notice No. GRN 000659. 2016; [cited 2019, October 29th] Available from: https://www.fda.gov/food/gras-notice-inventory/agency-response-letter-gras-notice-no-grn-000659.
19. FDA UFaDA. Agency Response Letter GRAS Notice No. GRN 000650. 2016; [cited 2019, October 29th]. Available from: https://www.fda.gov/food/gras-notice-inventory/agency-response-letter-gras-notice-no-grn-000650.
20. Davis JC, Lewis ZT, Krishnan S, et al. Growth and morbidity of Gambian infants are influenced by maternal milk oligosaccharides and infant gut microbiota. Sci Rep. 2017;7:40466.
21. Marcobal A, Barboza M, Sonnenburg ED, et al. Bacteroides in the infant gut consume milk oligosaccharides via mucus-utilization pathways. Cell Host Microbe. 2011;10(5):507-14.
22. Hoeflinger JL, Davis SR, Chow J, Miller MJ. In vitro impact of human milk oligosaccharides on Enterobacteriaceae growth. J Agric Food Chem. 2015;63(12):3295-302.
23. EC. Commission implementing regulation (EU) 2017/2470 of 20 December 2017 establishing the Union list of novel foods in accordance with regulation (EU) 2015/2283 of the European Parliament and of the council on novel foods. Official Journal of the European Union 2017;L 351/72:130.
24. Steenhout P, Sperisen P, Martin F-P, et al. Term infant formula supplemented with human milk oligosaccharides (2′Fucosyllactose and Lacto-N-neotetraose) shifts stool microbiota and metabolic signatures closer to that of breastfed infants. FASEB J. 2016;30(1 Suppl):257.257.
25. Berger B, Sprenger N, Grathwohl D, Alliet P, Puccio G, Steenhout P. Stool microbiota in term infants fed formula supplemented with synthetic human milk oligosaccharides is associated with reduced likelihood of medication. J Pediatr Gastroenterol Nutr 2016;62(Suppl 2):S406.
26. Puccio G, Alliet P, Cajozzo C, et al. Effects of infant formula with human milk oligosaccharides on growth and morbidity: a randomized multicenter trial. J Pediatr Gastroenterol Nutr. 2017;64(4):624-31.
27. Goehring KC, Marriage BJ, Oliver JS, Wilder JA, Barrett EG, Buck RH. Similar to those who are breastfed, infants fed a formula containing 2'-fucosyllactose have lower inflammatory cytokines in a randomized controlled trial. J Nutr. 2016;146(12):2559-66.
28. Netea SA, Messina NL, Curtis N. Early-life antibiotic exposure and childhood food allergy: a systematic review. J Allergy Clin Immunol. 2019;144(5):1445-8.
29. Obiakor CV, Tun HM, Bridgman SL, Arrieta MC, Kozyrskyj AL. The association between early life antibiotic use and allergic disease in young children: recent insights and their implications. Expert Rev Clin Immunol. 2018;14(10):841-55.
30. Rasmussen SH, Shrestha S, Bjerregaard LG, et al. Antibiotic exposure in early life and childhood overweight and obesity: a systematic review and meta-analysis. Diabetes Obes Metab. 2018;20(6):1508-14.
Please rotate your device
We don't support landscape mode. Please go back to portrait mode for the best experience.