Human Milk Oligosaccharides – an introduction


Human milk oligosaccharides (HMOs) are the third most abundant solid component in breast milk after lactose and fat. They are a diverse group of bioactive carbohydrates, composed of various combinations of the following building blocks: galactose, glucose, N-acetylglucosamine, fucose, and N-acetylneuraminic acid (a sialic acid derivative).


There are about 20 major HMOs in human milk.1 Of these, a specific HMO called 2’-fucosyllactose or 2’-FL is the most abundant HMO in a majority of mothers’ milk.2 2’-FL has been extensively studied and emerging research suggests it is the most bioactive and multi-functional HMO.3-6 2’-FL is a trisaccharide comprised of 3 units: glucose, galactose and fucose.1



HMOs resist digestion by human pancreatic enzymes and intestinal brush border enzymes in the upper gastrointestinal tract. Evidence suggests that the majority of HMOs reach the large intestine intact.7,8 Once HMOs pass into the large intestine, they are hydrolyzed and then fermented by intestinal microbiota to form short-chain fatty acids. Some may also be expelled in feces. A small portion of ingested HMOs are absorbed intact into the circulation and excreted in the urine9


HMOs, like 2’FL, play multiple roles to help protect baby’s digestive and immune health:10,11

  • They are prebiotics that selectively promote the growth of beneficial gut bacteria, including certain species of Bifidobacterium
  • They act as receptor decoys to prevent pathogens from adhering to cell surfaces. HMOs structurally resemble the sugars that bacteria use to cause infections, so they function as soluble decoys that block the attachment of potentially pathogenic bacteria
  • As HMOs are absorbed in circulation, they have the ability to bind to cell surfaces and trigger cells to release protective factors – acting as immune cell modulators
HMO-infection HMO-inflammation

 Emerging science also suggests that HMOs may exert positive health benefits on food allergies, brain development, and necrotizing enterocolitis (NEC).10,11

Pediatric nutrition and 2’-FL HMO

Recent research examined the growth and tolerance of healthy term babies fed formulas containing synthesized 2’-FL.12 The trial was a prospective, randomized, controlled, growth and tolerance study that enrolled 420 healthy term babies with gestational age of 37-42 weeks and birth weight of ≥2,490 g. They were randomized to receive one of three ready-to-feed formulas: one with 0.2 g/L of 2’-FL, another with 1 g/L of 2’-FL, and a control formula without 2’FL.

After four months of feeding, infants who were fed the 2’-FL supplemented formulas exhibited growth rates that were similar to babies who were fed the control formula. The 2’-FL supplemented formulas were also well tolerated. 2’-FL was present in the plasma and urine of babies fed the supplemented formulas, and there were no significant differences in 2’-FL uptake relative to the concentration fed.

Another aim of this clinical trial was to assess whether addition of 2’-FL to infant formula impacted biomarkers of immune function.13 At six weeks, blood samples were obtained. Babies fed either of the experimental formulas with 2’-FL were not different but had lower concentrations of plasma inflammatory cytokines [interleukin (IL) receptor antagonist (IL-1ra), IL-1a, IL-1b, IL-6, and tumor necrosis factor α (TNF- α)] (P ≤ 0.05) than did infants fed the control formula.

1.Chen X. Adv Carbohydr Chem Biochem. 2015;72:113-90.
2. Erney RM, et al. J Pediatr Gastroenterol Nutr, 2000. 30(2):181-92.
3. Ballard O, et al. Pediatric Clinics of North America. Feb 2013;60(1):49-74.
4. Vazquez E, et al. J Nutr Biochem 2015; 26(5):455-465.
5. Good M, et al. Br J Nutr 2016; 116(7):1175-1187.
6. Castillo-Courtade L, et al. Allergy 2015; 70(9):1091-1102.
7. Engfer MB, et al. Am. J. Clin. Nutr. 2000;71(6):1589-1596.
8. Gnoth MJ, et al. J. Nutr. 2000;130(12):3014-3020.
9. Rudloff S, Kunz C. Adv. Nutr. 2012;3(3):398S-405S.
10. Bode L. Glycobiology. 2012;22(9):1147-62.
11. Castanys-Munoz E, et al. Nutr Rev, 2013. 71(12):773-89
12. Marriage BJ, et al. J. Pediatr. Gastroenterol. Nutr. 2015;61(6):649-658.
13. Goehring KC, et al. J Nutr. 2016;146(12):2559-2566.

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