What Are Human Milk Oligosaccharides (HMOs)?

Written by

Tiny Health Team

Medically reviewed by

Meghan Azad, PhD

Scientifically reviewed by

Meghan Azad, PhD

Summary

HMOs are a type of milk sugar found in mom’s breastmilk.
HMOs go undigested through your baby's digestive tract and feed your baby’s gut microbes.
HMOs can reduce the risk of viral and bacterial infections and help develop your baby’s immune system.
While breastmilk is the better option, some infant formulas now contain HMOs.

Human milk oligosaccharides, or simply HMOs, are milk sugars that are found in your breastmilk. Breastmilk contains more than 200 different types of HMOs [1]. Just like a fingerprint, your HMO profile is unique.

HMOs are a chemical variation of the milk sugar, lactose. All HMOs are made up of a combination of smaller sugars, which includes:

Glucose
Galactose
Fucose
N-acetylglucosamine (GlcNAc)
Sialic acid (N-acetylneuraminic acid) sugars [2]

After lactose and fats, HMOs are the third most abundant component of breastmilk - even more abundant than protein.

There are three major types of HMOs in human breast milk, including:

Fucosylated HMOs
Sialylated HMOs
Non-Fucosylated neutral HMOs [3]

These HMOs differ in the presence or absence of different sugar molecules, such as fucose.

How are human milk oligosaccharides (HMOs) made?

HMOs are unique in that they are made by moms. There are several factors that may influence a mom’s ability to make HMOs, including geographical location and her genetics [4].

This means that HMO levels vary from mom to mom.

But it gets a little more complex.

All moms have a specific gene that helps with the creation of certain HMOs: the fucosyltransferase 2 (FUT2) gene. This gene encodes the enzyme 2-α-L-fucosyltransferase 2, which helps form a particular linkage in certain HMOs.

However, in some moms, the FUT2 gene is inactive.

Moms with active FUT2 genes are known as “secretors.” While moms without the active FUT2 genes are known as “non-secretors.”

Secretors are able to create the FUT2 enzyme that helps add on the fucose sugar in a particular biochemical linkage found in certain HMOs, including 2′-fucosyllactose (2’FL).

Among secretors, 2’FL is typically the most abundant HMO in breastmilk [3]. Whereas non-secretors do not make the FUT2 enzyme necessary to make HMO 2’FL.

Research shows that about 20% of Caucasians are “non-secretors” [5]. Though this isn’t without its benefits. For example, non-secretors can have more resistance to certain unfriendly viruses, including norovirus and rotavirus [5]. This may help decrease the risk of diarrhea.

However, the impacts of a mom’s secretor status are not clear and still being explored, as researchers try to understand how secretor status influences HMOs and babies.

The benefits of human milk oligosaccharides (HMOs)

1. HMOs increase beneficial bacteria

Though HMOs are present in your breastmilk, they do not provide nutrition for your baby. This is because HMOs go undigested through your baby's digestive tract [7]. But this is good. This feeds your baby’s gut microbes.

HMOs provide energy for beneficial bacteria, such as members of the Bifidobacterium and Bacteroides genera [6], [7]. These beneficial bacteria feed on HMOs through a process called fermentation.

Bacteria ferment HMOs and produce beneficial by-products called short-chain fatty acids (SCFA). SCFA are metabolites that have been shown to improve gut health by helping:

Maintain gut integrity
Produce mucus
Protect against inflammation [8]

This explains why the gut microbiome of breastfed babies is dominated by beneficial Bifidobacterium [2]. Breastmilk contains high levels of HMOs that Bifidobacterium are able to ferment. This is a good thing. HMOs can help boost beneficial bacteria, which can help crowd out potentially unfriendly bacteria.

2. HMOs improve your baby’s immune system

Because HMOs reduce the risk of viral and bacterial infections, they can directly influence your baby's immune system.

Research has shown that HMOs improve your baby's immune system by:

Fighting unfriendly microbes
Altering gene expression in certain cells [9]
Reducing unfriendly microbes

Not only do HMOs help promote beneficial bacteria that crowd out the unfriendly bacteria, but also have been found to have a unique antibacterial or antiviral role against certain microbes [10].

This can be seen with Streptococcus agalactiae, also called group B Streptococcus or GBS, which is an important unfriendly gut bacteria for babies. HMOs have been found to stop the growth of these bacteria [10].

Similarly, breastmilk has been shown to protect against rotavirus, which causes watery diarrhea and vomiting in babies aged 0 to 12 months old [11]. It’s thought that the HMOs in breastmilk are able to directly attach to certain viruses and prevent them from invading [13].

This shows that breastmilk and HMOs have protective properties for your baby.

HMOs and infant formula

The importance of HMOs to your baby's gut microbiome is so great that infant formula companies have now started to add them. The most common HMOs you will see added to infant formula are:

2’ -fucosyllactose (2’-FL)
Lacto-N-neotetraose (LNnT)

The most common HMO you will see added to infant formula is 2’ -fucosyllactose (2’-FL). 2′-fucosyllactose (2′-FL) is made up of the combination:

Glucose
Galactose
Fucose [3]

And we do see benefit from the small amount of HMO added to baby formula.

For example, a randomized control study followed babies who were either exclusively breastfed or given a formula that contained 2'-FL. Babies fed an infant formula containing 2′-FL had an anti-inflammatory response that was similar to the exclusively breastfed babies [12]. Though breastfed babies still tended to have lower inflammatory biomarkers.

Breastmilk HMOs vs Infant formula HMOs

Although some infant formulas now contain HMOs, breastmilk is still a better option, if it is possible. It’s free. It’s natural. It’s your own.

Here’s why.

Breastmilk adjusts over time to provide the right amount of nutrients for your baby as their needs change while they grow and develop.

It also contains different amounts of HMOs over weeks and months of breastfeeding. This can be seen in colostrum, the first breastmilk after birth, which is especially rich in HMOs. Levels go as high as 20.0 g/L - 25.0 g/L, while levels in mature milk can decrease as to 5.0 g/L – 20 g/L [13].

Individual HMOs also continue to change in concentration over the course of lactation. Many decrease and a few increase, reflecting their unique roles at different stages of baby development.

Unfortunately, these dynamic changes cannot be replicated in a one-size-fits-all formula.

Infant formula is often completely absent of HMOs. Even newer formulations that include HMOs only provide a relatively small amount relative to what you find in breastmilk and only contain one or two unique HMOs, compared to the hundreds found in breastmilk.

While manufacturers of infant formulas work hard to make a product that is increasingly similar to breastmilk, the gut microbiota of breastfed and formula-fed babies still remains very different [14].

That said, whether you feed your baby formula, breastmilk, or a combination of the two– HMOs can help your baby's gut microbiome along the way!

References

[1] N. J. Andreas, B. Kampmann, and K. Mehring Le-Doare, “Human breast milk: A review on its composition and bioactivity,” Early Hum. Dev., vol. 91, no. 11, pp. 629–635, Nov. 2015, doi: 10.1016/j.earlhumdev.2015.08.013.

[2] M. Wiciński, E. Sawicka, J. Gębalski, K. Kubiak, and B. Malinowski, “Human Milk Oligosaccharides: Health Benefits, Potential Applications in Infant Formulas, and Pharmacology,” Nutrients, vol. 12, no. 1, p. E266, Jan. 2020, doi: 10.3390/nu12010266.

[3] S. M. Totten et al., “Comprehensive profiles of human milk oligosaccharides yield highly sensitive and specific markers for determining secretor status in lactating mothers,” J. Proteome Res., vol. 11, no. 12, pp. 6124–6133, Dec. 2012, doi: 10.1021/pr300769g.

[4] M. B. Azad et al., “Human Milk Oligosaccharide Concentrations Are Associated with Multiple Fixed and Modifiable Maternal Characteristics, Environmental Factors, and Feeding Practices,” J. Nutr., vol. 148, no. 11, pp. 1733–1742, Nov. 2018, doi: 10.1093/jn/nxy175.

[5] D. Muthumuni, K. Miliku, K. H. Wade, N. J. Timpson, and M. B. Azad, “Enhanced Protection Against Diarrhea Among Breastfed Infants of Nonsecretor Mothers,” Pediatr. Infect. Dis. J., vol. 40, no. 3, pp. 260–263, Mar. 2021, doi: 10.1097/INF.0000000000003014.

[6] D. A. Sela and D. A. Mills, “Nursing our microbiota: molecular linkages between bifidobacteria and milk oligosaccharides,” Trends Microbiol., vol. 18, no. 7, p. 298, Jul. 2010, doi: 10.1016/j.tim.2010.03.008.

[7] A. Marcobal et al., “Bacteroides in the infant gut consume milk oligosaccharides via mucus-utilization pathways,” Cell Host Microbe, vol. 10, no. 5, pp. 507–514, Nov. 2011, doi: 10.1016/j.chom.2011.10.007.

[8] Y. P. Silva, A. Bernardi, and R. L. Frozza, “The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication,” Front. Endocrinol., vol. 11, 2020, doi: 10.3389/fendo.2020.00025.

[9] R. Akkerman, M. M. Faas, and P. de Vos, “Non-digestible carbohydrates in infant formula as substitution for human milk oligosaccharide functions: Effects on microbiota and gut maturation,” Crit. Rev. Food Sci. Nutr., vol. 59, no. 9, pp. 1486–1497, 2019, doi: 10.1080/10408398.2017.1414030.

[10] A. E. Lin et al., “Human milk oligosaccharides inhibit growth of group B Streptococcus,” J. Biol. Chem., vol. 292, no. 27, pp. 11243–11249, Jul. 2017, doi: 10.1074/jbc.M117.789974.

[11] A. Plenge-Bönig, N. Soto-Ramírez, W. Karmaus, G. Petersen, S. Davis, and J. Forster, “Breastfeeding protects against acute gastroenteritis due to rotavirus in infants,” Eur. J. Pediatr., vol. 169, no. 12, pp. 1471–1476, Dec. 2010, doi: 10.1007/s00431-010-1245-0.

[12] K. C. Goehring, B. J. Marriage, J. S. Oliver, J. A. Wilder, E. G. Barrett, and R. H. Buck, “Similar to Those Who Are Breastfed, Infants Fed a Formula Containing 2’-Fucosyllactose Have Lower Inflammatory Cytokines in a Randomized Controlled Trial,” J. Nutr., vol. 146, no. 12, pp. 2559–2566, Dec. 2016, doi: 10.3945/jn.116.236919.

[13] L. Bode, “Human milk oligosaccharides: every baby needs a sugar mama,” Glycobiology, vol. 22, no. 9, pp. 1147–1162, Sep. 2012, doi: 10.1093/glycob/cws074.

[14] A. M. Baumann-Dudenhoeffer, A. W. D’Souza, P. I. Tarr, B. B. Warner, and G. Dantas, “Infant diet and maternal gestational weight gain predict early metabolic maturation of gut microbiomes,” Nat. Med., vol. 24, no. 12, pp. 1822–1829, Dec. 2018, doi: 10.1038/s41591-018-0216-2.