The potential of human milk oligosaccharides to impact the microbiota-gut-brain axis

Mum breastfeeding baby_illustration

Human milk oligosaccharides (HMOs) are the first prebiotics we humans meet in life and are being explored for their potential in both infant and adult nutrition.

This blog explores what captured the interest of the Verve Journal Club when we discussed a literature review published in September 2020. We also share our thoughts and opinions on the potential of HMOs for future use. 


‘The potential of human milk oligosaccharides to impact the microbiota-gut brain axis through modulation of the gut microbiota’

View the full paper here.

The paper explored the gut microbiota, the microbiota-gut-brain axis formed by this, and the role human milk oligosaccharides can play in this. 

Section 1 — HMOs and their production

HMOs are sugar molecules and are the third most abundant component of human milk after lactose and lipids. They are composed from five monosaccharides, and around 200 distinct structures have been identified.

Traditionally HMOs were the reserve of breastfed infants, however, some can now be produced industrially. Of these, 2’-fucosyllactose (2’-FL) and Lacto-N-neotetraose (LNnT) are the most widely studied in humans. 


Mass production of HMOs could lead to their use in the treatment of diseases connected to the gastrointestinal system along with those affected by the microbiota-gut-brain axis.

The most obvious use of HMOs is in infant formula, closing the gap to the nutritional value of human milk, and this is already starting to be seen.

Section 2 — How the gut microbiota can impact the brain 

The gut microbiota can affect the brain in a variety of different ways, including through the neurologic, immunologic or endocrine pathways. 

Another route is by the regulation and production of numerous neuroactive biomolecules such as tryptophan and gamma-aminobutyric acid (GABA). 


Because the gut microbiota is linked to the central nervous system (CNS) it may present future targets for the treatment of conditions linked to the CNS including depression and Alzheimer’s disease. 

Section 3 — Modulation of the microbiota-gut-brain axis through the diet

Diet has been shown to be one of the most potent modulators of the gut microbiota, with varying global diets leading to significantly different gut microbiota profiles. 

Animal studies have shown that dietary supplementation with sialic acid (one of the building blocks of HMOs), can lead to increased learning and memory in piglets. 


Diet presents an interesting therapeutic target and while the benefits of a good diet and the healthy microbiota associated with it can be clearly seen, more research is needed to allow diet to be used in treating specific conditions.  

Additionally, the full impact and mechanisms of the gut-brain axis are not yet understood and, while the diet could influence some conditions, the level of effect is still up for debate.

Milk bottle near kid hands

Section 4 — HMOs and their impact on the gut microbiota and potential to affect the microbiota-gut-brain axis 

HMOs induce growth of beneficial bacteria species, (e.g. Bifidobacterium spp.), which are involved in the production or activation of important biomolecules such as short chain fatty acids (SCFAs), GABA, and ferulic acid (FA). 

In infants, it has been shown that 2’-FL and LNnT are safe, well tolerated, and could shift the gut microbiota, in particular by increasing bifidobacteria and promoting a microbiota phenotype closer to that seen in breastfed infants.

In CNS conditions such as Alzheimer’s disease and autism spectrum disorder an altered microbiota composition is seen with particularly decreased levels of Bifidobacterium.

In vitro and in vivo studies suggest a role for HMOs in modulation of the gut microbiota. However, clinical trials investigating this are still in their infancy. 


Evidence for the benefits of HMOs on the gut microbiota is clear and well-studied in infants, and so are beginning to be used in some formulas to promote a healthy gut in formula-fed infants. 

However, whilst their safety in infant formulae is well documented, the impact of their addition is not yet fully proven.  

There is also a clear suggestion that HMOs may become a useful tool in the management of CNS conditions which are linked to neuroactive biomolecules regulated and produced in the gut.

It is not yet clear how effective HMOs would be in this role, or which conditions will respond well to their use, and so further study is required. There are also some reservations in regard to how patients may react to dietary supplementation with a product closely associated with, and found in, human milk. 

Section 5 — HMOs and their effect in brain health and function

Studies have shown that breastfed infants show better cognitive results compared to formula-fed infants. Part of this effect could be due to HMOs. 

Several animal studies have examined the impact of HMOs directly or indirectly on brain health and function. They have shown that 2’-FL increased long-term potentiation (LTP) in rats and improved learning and memory skills. 


Human milk is known to provide infants with the best possible start in life, and as such, efforts must be made to bring formulas closer to breast milk in both formulation and effect on the infant. HMOs provide a straightforward next step in the development of infant formulas.


The paper provided a good insight into the pathways found between the gut microbiota, brain and immune health, along with the potential to modulate these pathways through the diet and the use of HMOs. 

HMOs have been heavily studied in animals, and the potential health benefits are clear to see. However, it was obvious that their use in adults is not well studied and further evidence is required before any direct/demonstrative health benefits can be claimed. 


Our monthly journal club is a great opportunity for us to keep up with the latest research in different therapy areas. It allows us to combine our HCP work with our passion for advances and knowledge in healthcare. 

The club is a chance for the team to come together to evaluate and discuss articles within pharmaceutical literature within a social environment.



Andrew Holloway Headshot
Andrew gained a BSc in Biochemistry with industrial experience and prior to becoming a Vervian worked in HCP guideline publishing. You won’t win a regulations argument against this man.

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