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HMOs bring infant formula one step closer to breast milk

Posted May 11

Five months ago, my wife and I brought our first child home from the hospital and began our crash course in parenthood together. At first, we fumbled through the routines of swaddling and diapering, which got easier with weeks of practice. Breast-feeding, on the other hand, did not. Gradually, we transitioned fully to feeding with formula.

Some version of this scenario is not unusual in the U.S., where the Center for Disease Control reports that 60 percent of 3-month-old infants are not breast-fed exclusively; by 6-months-old, this number rises to about 81 percent.

Feeding with an alternative to breast milk is also not anything new. There is evidence that, even as far back as 4,000 years before baby formula was created, our ancient human ancestors were turning to milk from various livestock to help sustain their infants. As far back as 38 years ago, I too was raised on mostly formula – just like my child. But a lot has changed since then.

The most recent development in the quest to bridge the biochemical gap between breast milk and bottle-feeding is the addition of human milk oligosaccharides to infant formula. As a new dad and biochemist, seeing HMOs in infant formula for the first time this year intrigued me.

HMOs are the third most abundant class of biomolecules in breast milk behind lactose and lipids (fats). Like fiber, an HMO could be described as a complex carbohydrate. More specifically, it is a lactose-based short chain of sugar molecules.

Unlike lactose and other constituents of breast milk, HMOs are nondigestible and appear to have no metabolic purpose for the infant. Until recently, this has made their abundance in breast milk somewhat of a mystery.

As it turns out, however, HMOs are a source of nutrition, just not for the infant.

During the past decade or so, scientific research has pried open the Pandora’s box of the human microbiome. Scientists have learned there are a lot of microbes living inside humans and our relationship with them appears to be far more symbiotic than we ever knew. This is especially important in the gastrointestinal system, where humans may have up to 1,000 different microbe species cohabitating with your gut.

But we aren’t born this way. The relatively sterile bellies of newborn babies are first populated with microbes acquired from mom via the messy process of child delivery, followed by breast-feeding, and eventually from fingers, toys, pacifiers and everything else that meets up with their mouths.

Among the first symbiotic colonizers of newborn bellies are various species from the bacterial genus Bifidobacterium. In this group, there are several species, and they are the most abundant microbes in both formula and breast-fed infants. Several other types of bacteria can be present in the infant gut as well, and the microbial demographics will vary from person to person, according to age and feeding mode.

We now understand that HMOs are a favorite snack for the Bifidobacterium and many of these other early colonizers that contribute to healthy digestive and immune systems.

In the same way that maintaining a healthy lawn precludes the growth of weeds, having a healthy amount of these benevolent microbes lining the intestines helps reduce the chances that more nefarious ones will be able to set up any gastrointestinal real estate. Because HMOs are a menu item for the good microbes but not the bad ones, HMOs are sometimes referred to as a prebiotic.

HMOs can also prevent infections from viruses (including norovirus and rotavirus) that often cause infants diarrhea or worse. They are able to neutralize these pathogens because they resemble the carbohydrate chains found on the surfaces of cells that viruses would otherwise latch onto before they infect.

As diverse as the microbes are that populate the infant gut, so too are the HMOs on which they feed. The number of different HMOs in human breast milk is estimated to be near 200, and their proportions vary from mother to mother and with stages of lactation.

For most women (but not all), the most abundant HMO in is called 2’-FL (2'-fucosyllactose). This is the HMO that now appears for the first time in infant formula commonly available in the U.S.

“While breast milk is clearly the best food for infants, it does make sense for formula manufacturers to adjust the composition when new ingredients, like HMOs, become available,” explained Robert Ward, associate professor of nutrition, dietetics and food sciences at Utah State University.

But at 17 to 26 cents per liquid ounce, the new formula that includes the 2’-FL HMO is among the most expensive on the supermarket shelf. Consumers evaluating this cost will want to evaluate if any of the benefits observed in breast milk can be replicated in formula supplemented with HMOs.

Some recent clinical studies are optimistic. Last year it was reported that infants fed with 2’-FL-supplemented formula showed immune profiles that were more similar to breast-fed infants than infants fed with standard formula.

Another study last year also reported a similar effect on the gut microbe profiles when formula was supplemented with 2’-FL and another HMO called LNnT (Lacto-N-neotetraose).

A study published this year also showed that supplementation with these two HMOs was associated with fewer reported incidences of respiratory infection and bronchitis.

These early studies were commissioned primarily by manufacturers of infant formula but, according to Ward, the studies are nevertheless useful.

“Formula is the most highly regulated item in the food supply, and these studies are important to provide evidence for improving its composition," Ward said.

"These studies appear to have been well conducted. The clinical trials were registered, and they are published in very respectable peer-reviewed journals. I understand why some might be concerned that they were funded by industry sources, but I am not sure it would have been feasible to get research support from either the U.S. Department of Agriculture or National Institutes of Health.”

It is likely parents will continue to see HMOs as an option in infant formula.

Although the dynamic complexity of a mother’s breast milk will always be an asymptote that formula continues to approach yet cannot reach, any step that brings it closer to that goal is good news for the many parents, like me and my wife, who depend on formula to keep their infant healthy, happy, growing and beautiful.

Robert Lawrence works in public health and writes about science. He studied biochemistry at the University of Utah and Arizona State University. You can follow his blog at www.cognitivefeedbackloop.com.

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