HMO Evolution in Human Milk

Can you tell us about your current research?

We have been studying human milk for many decades, and recently discovered that it contains indigestible material, which was very interesting. Mothers appear to be synthesizing molecules that go right through the baby. We decided to investigate this in detail.  We found that human milk contains an awful lot of carbohydrate oligosaccharides that are not digested.

How much is a lot?

Interestingly, oligosaccharides make up around a third of the contents of human milk. There is as much oligosaccharide as protein.

Is it stable during the period of lactation or does it change?

It is a generally constant feature. Colostrum has elevated levels, but thereafter it remains stable.

What did you think when you discovered this and what did you do?

First, we had to ask, why were mothers making milk with content that the baby could not digest. Then we wondered if bacteria could eat it. So, we isolated the oligosaccharides and we tested to see if bacteria would grow on it.  In the main they did not, but we did eventually find one strain of the Bifidobacterium which has an enzyme that could break it down.  This is remarkably beneficial bacteria, which is present because of the oligosaccharides. So, scientists around the world are trying to understand the benefits of this process that came out of evolution, where mothers provide food not only for the baby but for this bacterium too.  The bacteria attach all along the baby’s intestines, to protect the infant from pathogens.

So, the “good” bacteria are blocking the “bad” bacteria?

Correct.  This bacterium and grows and produces short-chain fatty acids and thus the ph. levels go down – the lower ph. value is again protecting the baby from pathogens.

Is this protection a local function in the gut?

Yes. The genius of milk is that molecules like this not only have two functions - binding to the baby and producing acetate - they also have responsibility for producing other metabolites that also nourish the baby.  The oligosaccharide molecules interact with the host directly and there is good evidence that they signal the baby’s immune system. 

How do they signal this?

It is very early days in research, but it looks like the immune system must decide between beneficial and benign, dangerous and pathogenic. That decision is based on signaling molecules. By producing molecules that tend to lower the activation of the immune system then you seem to move towards an immune system that is better for the baby.

You also see these molecules signaling the intestinal cells to start forming the natural barriers between cells that babies must develop as they mature.

Does this mean that the baby is also protected against allergies?

The most provocative outcome of this science to date is that one of the problems of the modern immune system of babies is that the immune system is inappropriately activated and reacts to molecules that it shouldn’t and forms an allergic reaction.

So, is this a wonder drug in mother’s milk?  Can it be copied and put into an infant formula?

Ultimately the goal is to make infant formula as close to human milk as possible. This is a dimension of human milk that is chemical and its composition can be reproduced. 

What would you expect as a clinical outcome of including oligosaccharides in formula?

The studies to determine all the benefits must be done over the coming years, but we do anticipate that the immune system would be improved. 

Ultimately we want to see more babies breastfed, but where that is not possible then this could be a way to improve the trajectory of the immune system.

Is it only important in the first two or three months, or could the protective effect last longer, perhaps during mixed feeding?

There is no clinical evidence now one way or the other.  We would speculate based on our results so far that the longer the babies can get the benefit probably the better.