What’s the latest in milk oligosaccharides?

The first year of life is a key phase in the development of the microbiome, with breastfeeding having the biggest influence in shaping the gut microbiome in early childhood. [1] Apart from protein, fat and lactose, breast milk also consists of oligosaccharides in concentrations that far exceeds that in cow’s milk.

Among the 150-200 human milk oligosaccharides (HMOs) identified to date, one of the most abundant human milk oligosaccharides (HMOs) in the milk of most women is 2’-fucosyllactose (2’FL). The concentrations of these HMOs vary widely among mothers.[2] Preliminary studies suggest that maternal factors, such as diet, exercise, illnesses, and probiotic consumption[3] may influence the HMO composition of breast milk.

Various HMOs have been associated with antimicrobial effects against pathogens, e.g. bacteria that cause diarrhoea.[4],[5],[6],[7] HMOs protect against pathogen colonisation and reduce the risk of infection not only by promoting the growth of beneficial bacteria, but also by exerting bacteriostatic or bactericidal effects on pathogens, such as group B Streptococcus.[8] HMOs have also been demonstrated to protect against enteropathogenic E coli by inhibiting their attachment onto the gut epithelial cells. Apart from these local effects in the gut, HMOs are also postulated to have systemic effects as immune cell modulators.

Several studies have also demonstrated that HMOs play a role in promoting growth during early infancy and childhood.[9],[10],[11] Concentrations of the HMO, 2’FL in the mother’s milk has also been correlated with cognitive development in the infant at 24 months of age.[12] Evidence also suggest that HMOs confer immunological effects,[13] with several HMOs implicated in reducing the risk of allergies, including cow’s milk allergy, food sensitisation.[14],[15],[16] Investigations are ongoing to develop targeted pre-, pro- and synbiotics with probiotics that utilise some HMOs, but not others that confer beneficial effects on the infant.

In summary, HMOs are the third most abundant component of human milk. They remain undigested by the host and reach distal parts of the gastrointestinal tract intact where they can serve as prebiotics but also have antimicrobial, antiadhesive, epithelial and immune cell modulatory effects. HMOs also enter systemic circulation where they may affect infant physiology, metabolism, immune system, etc. Different HMOs confer different health benefits and opportunities exist to develop pre-, pro- and synbiotics with probiotics that feed off specific HMOs and yet leave other HMOs with beneficial effects intact.

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[1] Stewart CJ, et al. 2018 Oct;562(7728):583-588.

[2] Azad MB, et al. J Nutr. 2018 Nov 1;148(11):1733-1742.

[3] Seppo AE, et al. JAMA Pediatr. 2019 Mar 1;173(3):286-288.

[4] Alliet P et al. Abstract accepted at the 6th WCPGHAN, June 2020, Copenhagen, Denmark.

[5] Lin AE, et al. J Biol Chem. 2017 Jul 7;292(27):11243-11249.

[6] Jantscher-Krenn E, et al. Br J Nutr. 2012 Nov 28;108(10):1839-46.

[7] Laucirica DR, et al. J Nutr. 2017 Sep;147(9):1709-1714.

[8] Lin AE, et al. J Biol Chem. 2017 Jul 7;292(27):11243-11249.

[9] Alderete TL, et al. Am J Clin Nutr 2015; 102(6): 1381-8.

[10] Lasrsson MW et al. Frontiers in Pediatrics 2019;7:297.

[11] Lagstrom H, et al. Am J Clin Nutr 2020;11(4):769-778.

[12] Berger PK, et al. PLoS ONE 2020; 15(2): e0228323.

[13] Triantis V, Bode L, van Neerven RJJ. Front Pediatr. 2018 Jul 2;6:190.

[14] Seppo AE, et al. J Allergy Clin Immunol 2017;139(2):708-711.

[15] Miliku K, et al. Allergy 2018;73(10)2070-2073.

[16] Lodge CJ, et al. J Allergy Clin Immunol. 2021 Mar;147(3):1041-1048.