Human Milk Oligosaccharides Functional Outcomes

What are oligosaccharides? Are they part of breast milk?

Human milk oligosaccharides (HMO) are complex sugars that mothers produce in very large quantities in their breast milk.  We can think of them as fibres, and the baby cannot consume them.  One of goals of the oligosaccharides is to alter the gut bacteria of the infant. 

Are they partially absorbed or not at all?  How do they work?

The gut does not process them.  They may make their way into the bloodstream, but it is not absorbed as a nutrient.

There is a function for almost every molecule in human milk.  One of the functions of the oligosaccharides involves direct stimulation of the immune system or interaction with human cells in a positive way.  Another interaction is to block pathogens or bacteria from binding to human cells.  Another interaction is to enrich in the colon specific beneficial bacteria.  Thus, there is multiplicity of function in human milk oligosaccharides.

How do human milk oligosaccharides influence the microbiota?

Like fibre does, HMO’s make it undigested into the colon.  In the colon, there is a subset of bacteria that can process those complex sugars and use them for food.  Those bacteria ferment the food and they can produce end products that are in turn food for the colonosites.

When we are born, we are somewhat sterile, and our intestinal tract becomes colonised by many different mechanisms: by the fact that we share some of our mother’s microbes and because we drink breastmilk which contains microbes.  In a sense, milk farms the microbiota in the child, and it helps raise the right microbes and helps to prevent the wrong microbes.

So, what is the HMO doing in the body?

It is helping to enrich a specific population of bifidobacteria, and this can be helpful in several mechanisms.  Bifidobacteria produce end products of fermentation, acetate and lactate, which is well known to lower the ph. of the colon.  This makes it difficult for other pathogens to grow in that same environment.  And it is consuming the only food available in that environment so other organisms have trouble gaining access. The short chain fatty acids, the acetate and lactate, are well known to stimulate the immune system in a positive way.  This is improving the barrier function of the colon.  Having a strong fermentation in the colon is associated with a healthy infant – this has been known for over a hundred years.

How about the pre-term, low birth weight infant?

In infants where the traditional colonisation of the intestinal tract has been disrupted, either due to early birth, or via the introduction of antibiotics, where the gut microbiota has been changed dramatically, you are going to see an assemblage to try to consume the HMOs if organisms are present that can actually do it.   Other organisms besides bifidobacteria can consume HMOs, but residual food can be left behind which may or may not be consumed by harmful bacteria.  So, in premature infants or others that might be dysbiotic, there is the chance that HMOs can actually cross-feed a population of bacteria that may have some associated risk.

What would be your criteria to establish safety if introducing HMOs into infant formula?

It needs a lot of thinking and additional science.  The idea is that we can get these complex HMOs that are naturally in breastmilk into formulas in the hope of generating a gut microbiota that is similar to that of a breastfed term infant.  This is what we want to achieve.  The safety concerns would include asking: what is the microbiota of the child you are delivering the food to?  What is the risk of cross-feeding or enriching a bacterial population that might pose a risk? 

It may be that infants in different parts of the world have different microbiotas and we need to understand their responsiveness to these types of introductions.

Would there be more risk in developing countries?

The irony of that is that populations in developing countries actually have more bifidobacteria than we see in more developed countries.  But more developed countries have less pathogens in their environment so we have less risk.  It needs to be equally studied in both populations. 

What would you be looking at, in terms of efficacy of formula products?

I would be looking at the microbiota shifts first of all.   I think we want to understand if the HMOs are beneficially feeding the bifidobacterial population.  We want to ensure that is reproducible.  We need to understand where there is no response as well.  It is going to take thorough analysis.