Unique Sugars in Human Milk Cut Infant Food Allergies

Written by: Anna Petherick, Ph.D. | Issue # 77 | 2018

Often, studies that investigate a possible association between breastfeeding and the development of allergies find one, but not every time. For many researchers this would simply suggest random variation in the world. However, for Kozeta Miliku, of the University of Manitoba, Canada, and her colleagues, the variation has sparked a new avenue of research. They have discovered that instead of being random, the suite of mid-sized sugar molecules that are present in an individual mother’s milk contribute to the probability of her infant having food allergies at the age of one [1]. Because the list and amount of these sugars varies from mother to mother, so does the extent to which human milk protects infants from developing allergies.

The unique sugar molecules in question are known as human milk oligosaccharides (HMOs). Curiously, these sugars make up a substantial proportion of the total solids in milk, which implies a metabolic cost to the mother’s body to produce them. Yet infants are unable to digest them. Together, these facts suggest that HMOs must have been maintained in human evolutionary history because they conferred survival advantages to infants other than direct nourishment.

The past decade or so has seen an uptick in research on these sugars. Investigators have shown, among other things, that HMOs prevent germs from finding a foothold on the gut wall, which is the first step to them entering human cells, and that they promote the bacterial colonization of the gut towards “good,” as opposed to pathogenic, bacteria.

Researchers have also found that the HMO profile of two different mothers’ milks can be quite different. Estimates of the total number of HMOs vary, and are typically in the range of 150 to 200. But the group of HMOs that are the most prominent in any individual woman’s milk is influenced by her health and the stage of lactation, as well as by her genetic ancestry. For example, a study published in 2017 found that one particular HMO called 2’-fucosyllactose was much more common in the milks of breastfeeding women living in the outskirts of Lima, Peru, and in Southern California than it was in the milks of women from in rural Gambia [2].

The new evidence that HMO profiles of milk can influence allergy development in infants comes from a cohort known as CHILD (Canadian Healthy Infant Longitudinal Development cohort), which includes 421 pairs of a mother and her infant. Miliku and her colleagues took samples of milk from the mothers enrolled in this study, and examined the levels of 19 different kinds of HMOs [1]. Specifically, the team used a technique called Projection on Latent Structures-Discriminant Analysis, which can work out the absolute amount of each HMO in each sample. They then followed the mother-infant pairs until the infants turned one year old. At that stage, 59 of the infants (or 14% of the total) were sensitive to at least one food allergen.

After crunching some statistics, the researchers concluded that only 10 out the 19 HMOs that they measured were important in predicting food sensitization among the year-old infants. In some cases, the influence was not slight. The Projection on Latent Structures-Discriminant Analysis enabled the researchers to work out a ranking of the HMOs according to their association with food sensitization, and from this they created “discriminant scores” for each mother’s milk, depending on the milk’s HMO profile. Infants whose mothers produced milk in the top 20% of the discriminant scores had a 90% lower risk of developing food allergies by their first birthday than infants whose mothers’ milks scored in the lowest 20%.

This is not the first examination of HMOs and food allergies. However, it is the first to assess the contribution of a reasonably long list of HMOs, and to draw a conclusion that the overall profile is what matters. A few other studies have probed the influence of individual HMOs, and concluded that the sugar 2’-fucosyllactose is important for this outcome in humans [3] and in rodents [4]. Although this sugar is on Miliku and coauthors’ list of 10 relevant HMOs for infant food allergy risk, it was not a significant contributor to this risk on its own.

These conclusions suggest that attempts to supplement infant formula with just one or two HMOs should really seek to cast the net much more widely. But it’s also early days to reach firm conclusions. The mechanisms by which HMOs could reduce the odds of food allergies are largely speculative, and based on related roles that science perhaps has not fully uncovered. It is a fertile area for future research.

References

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