Researching human milk oligosaccharides

Scientists are learning more about how human milk oligosaccharides (HMO) work in infants - which could lead to new ways to prevent disease.

When looking at the make-up of breast milk, human milk oligosaccharides (HMO) come in 3rd place - after lactose and lipids. Simply due to their abundance, it would seem obvious that HMOs are important to growing babies. Now studies into these complex, indigestible sugars are revealing their structures - and helping to explain how HMOs work to prevent disease and promote a healthy microbiome in babies.

The different types of sugars that make up the HMOs act as probiotics, to feed the good bacteria in baby's intestines. Research shows that 1% of HMOs find their way into the circulatory system - while the other 99% are used by the intestinal microbiome (or end up in baby's diaper). It is also possible that certain components of HMOs are absorbed through the tonsils while baby is drinking - which is believed to offer protection from viral respiratory illness.

HMO investigations

In their 2020 article, Human Milk Oligosaccharides: Health Benefits, Potential Applications in Infant Formulas, and Pharmacology, researchers investigated how HMOs work, and ways they help prevent disease - including viral and bacterial infections.

Mothers are the source of  HMO, and their introduction to her newborn begins with the first feedings of colostrum. This contains the highest level of HMO (20-23 g/L) - which is even higher in the milk of mothers giving birth to preterm babies.

One could assume that, given the protective benefits offered by HMO, the higher levels of HMO in preterm milk offers even more protection to these vulnerable and often underweight babies. But assumptions are not the way of science - they are merely the inspiration behind research. And the precise ways that the approximately 200 different HMOs work still needs to be studied.

Pathogens and parasites

One effect that has been studied is anti-adhesion - a way of tricking pathogens into attaching to an HMO instead of a human cell surface. So instead of a dangerous norovirus or rotavirus attaching itself to a cell - then multiplying and causing disease - the pathogen attaches to an HMO and is safely exits the baby in urine or feces. This discovery could lead to new therapies to fight these viral infections, as studies show that adding HMOs to food can help fight noroviruses.

The ability of HMOs to block adhesion of pathogens may also include entamoeba histolytica, the parasite that causes amoebic dysentery. The ability to prevent this parasite from attaching to cells may be the key to lower rates of amoebic dysentery in breastfed babies (compare with formula-fed babies).

Animal studies also show a protective function of HMOs in preventing or treating necrotizing entereocolitis (NEC) - a severe (and possibly fatal) intestinal infection that affects 5-10% of low-weight premature babies. More research is needed, but the hope is that these animal studies can be replicated in humans.

Microbiome formation

HMOs are important for the formation of a baby's microbiome, working as a probiotic to feed the intestinal bacteria that colonizes the intestines. Of the different types of bacteria in infant intestines, bifidobacteria should dominate, which is the case in breastfed babies. Bifidobacteria ferments HMOs - which lowers the pH of the intestines - and helps stop pathogens from multiplying.

HMOs also help boost the production of short chain fatty acids - which play a key role in activating immune cells, and form a source of energy for the intestinal absorptive cells (responsible for the absorption of nutrients and water).

HMOs in formula

Breastfed babies have less incidences of diseases such as diarrhea, respiratory infections, urinary infections, otitis media and necrotizing entereocolitis. Breastfeeding also reduces incidences of immune-related diseases, including celiac disease, asthma, allergies, and type 1 diabetes. But what about formula-fed babies?

While the full range of HMOs are not included in infant milk formulas, the HMO known as 2-fucosyllactose (2'-FL HMO) is starting to be being added to formula for its immune support - as is the HMO, lacto-N-neotetraose (LNnT). This is good news for mothers who are unable to breastfeed.

Studies show that 2'-FL HMO may reduce diarrhea associated with campylobacter jejuni. LNnT has been shown to reduce the number of streptococcus pneumonia cells (in animal testing). Results of studies show an improvement in the levels of intestinal flora, which was seen as similar to breastfed babies.

Scientists are continuing to study HMOs and how they work. The more they learn, the better HMOs can be used to target specific conditions - in both infants and adults. The addition of more HMOs in formula can prove very beneficial to newborns, as well. So they can grow healthy while enjoying the same benefits seem in breastfed babies.