Commentary: Role of HMOs in Infant Nutrition

HMOs are complex carbohydrates found in breast milk1 which are utilized by certain strains of bacteria such as bifidobacteria and allows their proliferation. HMOs have been shown to indirectly affect infants’ immune systems via promotion of gut health. HMOs are antimicrobial and prevent pathogen colonization. HMOs also promote the growth of beneficial bacteria, in particular, Bifidobacteria, which help to restore immune markers and the intestinal barrier. Besides indirect effects, it has been suggested that HMOs can also directly modulate immune response by binding directly to immune cells. Clinical trials showed that infants fed with formulas supplemented with 2’FL had a gut microbiota that more closely resembled those of breastfed infants than the control-fed infants. This shows that the gut microbiome of infants can be positively influenced through the consumption of infant formula with HMOs. Supplementation of infant formula with HMOs has been associated with multiple health benefits.

What are HMOs?

HMOs are complex carbohydrates found in breast milk1 which are utilized by certain strains of bacteria such as bifidobacteria and allows their proliferation.2-3 Over a hundred HMOs have been identified but their composition vary between individuals, due to genetic and possibly environmental factors.1 An example of a common HMO is 2′-fucosyllactose (2′FL), which is found in high concentrations in women with actively expressed FUT2.4

HMOs are absent in majority of standard cow milk-based infant formulas.1,3 Hence, galactooligosaccharides (GOS) and fructooligosaccharides (FOS) were developed, which mimic the prebiotic effect of breast milk and are reasonable additions to improve the quality of infant formulas.3 However, GOS and FOS are simpler structures compared to HMOs which are complex glycans.3 HMOs have immunomodulatory and anti-inflammatory effects which GOS and FOS cannot mimic. Therefore, exclusive breastfeeding for the first 4 to 6 months of an infant’s life is recommended.

 

What is the role of HMOs on immune development in infants?

HMOs have been shown to indirectly affect infants’ immune systems via promotion of gut health. HMOs are antimicrobial and prevent pathogen colonization. For example, they inhibit the growth of group B Streptococcus (GBS),5 which can be passed from mother to infant during delivery and may cause infection during the first week of life.5 HMOs also promote the growth of beneficial bacteria, in particular, Bifidobacteria,3 which help to restore immune markers and the intestinal barrier.6 Besides indirect effects, it has been suggested that HMOs can also directly modulate immune response by binding directly to immune cells.3

 

Are there benefits to supplementing infant formula with HMOs?

Infant formulas with 2’FL added have shown promising results.7 Supplementing infant formula with HMOs would be beneficial in cases where infants cannot be exclusively breastfed for the first 4 to 6 months.

Oligosaccharides are bifidogenic agents. This means that HMOs are fermented by bifidobacteria and promotes their growth.3 In vaginally delivered infants who are breastfed, bifidobacteria predominate the gut microbiota.3 Clinical trials showed that infants fed with formulas supplemented with 2’FL had a gut microbiota that more closely resembled those of breastfed infants than the control-fed infants .7 This shows that the gut microbiome of infants can be positively influenced through the consumption of infant formula with HMOs.

HMOs have also been suggested to prevent allergic disease. Sialyated HMOs were shown to reduce IL-4 production in peanut allergy.3  Other studies suggest HMOs can reduce food allergy symptoms by inducing IL-10 regulatory cells and indirect mast cell stabilization.3 HMOs can also inhibit the release of chemokines induced by inflammation.3

Besides these benefits, HMOs have also demonstrated antiviral potential, protecting against rotavirus and norovirus infections, influenza viruses and mother-infant human immunodeficiency virus transmission.3 By promoting the maturity of infants’ immune systems, HMOs have also been associated with lower incidences of diseases such as asthma, type 1 diabetes and leukemia.3 Hence, there are multiple benefits to supplementing infant formula with HMOs apart from gastrointestinal benefits.

Breast-fed infants have been shown to have different growth patterns from formula-fed infants, with formula-fed infants having a lower fat mass at 3 to 4 and 6 months.8 However, HMOs have been shown to promote growth during early infancy.9-11 Supplementation of infant formula with HMOs may promote growth patterns similar to those seen in breastfed infants.

 

What are some of the current research gaps pertaining to the use of HMOs?

Oligosaccharides have been shown to promote healthy gut microbiota and improve the immune system in infants. The potential of HMOs may go beyond these benefits and research in multiple areas are still ongoing.3 For example, these benefits could be expanded to older children or adults with gastrointestinal disorders, by promoting the growth of beneficial bifidobacteria in the gut.12 However, there will be more confounders to consider in the older age group due to increased variance of food sources in the adult diet.

While prebiotic oligosaccharides have been identified and added into infant formulas, the composition of breast milk still cannot be replicated. More research is needed to study its biologically active components.3

 

References

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

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

3.       Wiciński M, et al. 2020 Jan 20;12(1):266.

4.       Bode L. Early Hum Dev. 2015 Nov;91(11):619-22.

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

6.       Ruiz L, et al. Front Microbiol. 2017 Dec 4;8:2345.

7.       Storm HM, et al. Glob Pediatr Health. 2019 Mar 15;6:2333794X19833995.

8.       Gale C, et al. Am J Clin Nutr. 2012 Mar;95(3):656-69.

9.       Marriage BJ, et al. J Pediatr Gastroenterol Nutr. 2015 Dec;61(6):649-58.

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

11.   Larsson MW et al. Frontiers in Pediatrics 2019;7:297.

12.   Šuligoj T, et al. Nutrients. 2020 Sep 13;12(9):2808.