New Insights on the Science of HMOs Part 1: how HMOs positively impact the development of the microbiome

Early life nutrition has implications for future health: experts weigh in  

• This is the first article in a 3-part series on the impact of human milk oligosaccharides (HMOS) on human health. The series will explore the role of HMOs in the microbiome, brain development, and immunity, as well as the evolving science around how HMOs might influence the gut-brain-immune axis.  
• HMOs are the third largest component of breastmilk (excluding water) after fat and lactose, suggesting this bioactive component could play a significant role in infant development and overall human health.¹ 
• There is a great desire to gain more knowledge on how HMOs might shape various elements of human health, namely, their impact on our microbiome or the collective community of microorganisms in the gut, on brain development, and on the immune system. Experts at dsm-firmenich weigh in on this topic, and in this article, Louise Kristine Vigsnæs, Head of Biology, and Stine Dam Jepsen, Scientist at dsm-firmenich, help enhance our understanding of how HMOs influence development of the microbiome.  

The significance of the microbiome and how HMOs impact its development  

Early life is a critical window for shaping and influencing the gut microbiota, which are the microorganisms that live in the GI tract, setting the stage for an aspect of our health that may impact several areas of development.^{2, 3}  The microbiota is considered to have a substantial influence on the overall health of the host, as well as on how the intestinal tract matures and functions.^{2, 4}   

While the science continues to emerge around the health benefits of HMOs, it is known that they reach the large intestine mostly undigested and serve as food for beneficial bacteria, supporting the development of a healthy community of bacteria, particularly bifidobacteria.^5-7  Since roughly 70% of immune system cells are housed in the gut, the influence of the microbiome may extend into the functionality of the immune system.^8,9  

How does a healthy gut microbiota support infant development?  

Louise Kristine Vigsnæs, Head of Biology at dsm-firmenich: The gut microbiota and its development in the infant is very important. Emerging evidence suggests it could play several roles, such as influencing GI tract development, maintaining mucosal integrity, impacting the nutritional status of the host, and helping to defend against undesirable microbes.¹⁰ 

A healthy gut microbiota can be quite important in developing a healthy immune system,  with preclinical and clinical research indicating that it helps the immune system determine which microbes are okay to be present and which should not be present in the host.^11,12 

In relation to protection against undesirable microbes, there are a few factors involved. First, when a healthy gut microbiota is predominant in the gut, there is little room for undesirable microbes to colonize it. Secondly, a healthy gut microbiota creates an environment which is not favorable for undesirable bacteria to grow.  

What are the implications when the microbiome development deviates from what is considered healthy or “typical”?  

Louise Kristine Vigsnæs: The development of the gut microbiota occurs during a critical window of time during infancy. A disturbance of the gut microbiota leads to an “out of balance” or unhealthy microbial community, which can lead to certain health implications.^2,10  Research suggests the gut microbiota, host, and the immune system work in a tight alliance, which means that they are dependent on each other and cannot work optimally if one or the other is compromised. Hence, if the gut microbiota is out of balance (e.g. after antibiotic treatment), the immune system may not react correctly, and this could lead to development of autoimmune diseases and allergies, as found in association studies.^13,14  

Certain factors have an impact on the gut microbiota composition and development, such as birth mode, early exposure to medications like antibiotics, and whether breastmilk or formula is used. These circumstances can have later implications to health outcomes.²

Describe the mechanisms of how HMOs impact the bacterial community in the GI tract. 

Stine Dam Jepsen, Scientist at dsm-firmenich: Early preclinical research indicates that HMOs may impact the gut bacterial community in different ways. First, they are non-digestible oligosaccharides, which means they can resist the impacts of gastric acid and enzyme hydrolysis in the gastrointestinal tract, avoid most systemic uptake, and selectively stimulate the growth of beneficial bacteria.^15,16 Second, by contributing to a beneficial gut microbiota by stimulating beneficial gut bacteria, they can help avoid colonization with undesireable microbes.^17,18 In addition, HMOs also have a positive effect on the gut wall barrier, resulting in favorable surroundings for a healthy gut microbiota. ^15,19  

What does the latest research show related to HMOs’ ability to impact development of the microbiome?  

Louise Kristine Vigsnæs: A large cohort study has shown that one of the significant factors associated with the gut microbiota and its development was the consumption of breast milk. The authors of the study imply that this is due to the presence of bioactive components in breast milk, including HMOs.20 In agreement with this, an earlier study has found that when comparing the gut microbiota of breastfed infants and infants fed formula without supplemented HMOs, the composition was quite different with less bifidobacteria in the formula fed infants.21 Bifidobacteria are beneficial bacteria and important for infant health.^22,23 

In a recent infant study using HMOs produced by Glycom/dsm-firmenich in infant formula, a positive impact was seen on the development of the gut microbiota, with a composition that came closer to that of breast-fed infants, including an increase in bifidobacteria.²⁴

HMOs: specific structures have specific functions 

At least 200 different HMOs have been identified in human milk.^1,25 These oligosaccharides are highly complex structures unique to human milk – no other mammal has near the concentration and complexity of these carbohydrate structures in their milk.²⁶ HMOs are one of the bioactive molecules in breastmilk, a group of compounds thought to have short- and long-term effects on infant development.^3,6 The amount and composition of HMOs varies between women and over the course of lactation.^27,28  It has been estimated that the production of HMOs by the mammary gland requires ten percent of the mother’s total energy expenditure for milk production.²⁹ Further, HMO functionality is structure-specific – not all HMOs serve the same purpose.³⁰ The human body’s investment in HMO production hints at an evolutionary motive for their manufacture and suggests significant benefits of HMOs may be likely to exist.  

Do all HMOs impact the microbiome the same way?

Louise Kristine Vigsnæs: We are still in the infancy of fully understanding the impact of the different structures of HMOs on the gut microbiota and on the host. Research has shown that some structures are better utilized by specific bacteria in the gut than others, implying that the other structures not utilized by the microbiota serve another purpose. Mom would not have produced all these HMO structures if they were not important for the infant! However, much more research is needed before we gain a fuller understanding. 

The gut-brain-immune axis: is there a role for HMOs? 

An exciting area of research in the field of HMOs is related to how these substances might impact the gut-brain-immune axis. The gut-brain-immune axis refers to the communication system that exists between the GI tract, central nervous system including the brain, and immune system. The functioning of each of these body systems impacts the others through pathways and biochemicals that carry messages back and forth to each other.^9,31 A mixture of preclinical and clinical research has shown HMOs can positively affect each of these systems.³ 

New research indicates the immune system should be added to the term gut-brain axis, creating the gut-brain-immune axis. How does the microbiota influence the brain and the immune system? 

Stine Dam Jepsen: The intestinal wall, gut microbiota, and immune cells are interconnected to each other.³² A slight disruption in one of these components can lead to unfavorable conditions such as dysbiosis or inflammation in the gut. The gut microbiota has a critical role in educating and regulating the immune system. A healthy and balanced microbiota is therefore essential for shaping a beneficial immune system and maintaining balance.³

The microbial community in the intestine also greatly impacts the brain; this is seen beyond infancy. For example, observational studies investigating brain disorders such as Alzheimer’s and Parkinson’s have found that these diseases can be associated with changes in the gut microbiota.33-35 Mechanistic research has found that the gut microbiota can impact the brain by several routes which include sending signals to the brain via bacteria-produced neuroactive molecules.^36,37 Hence, the gut microbiota is highly linked to brain health.^3, 38

The potential of HMOs – looking ahead 

As experts in HMOs, in what areas do you believe they have the most potential to influence health?

Louise Kristine Vigsnæ and Stine Dam Jepse: We believe that HMOs have great potential, not only for infant health but also for older kids, adults and the elderly. Because of their modes of action and proposed benefits, we believe HMOs could influence several health areas outside the gut, such as systemic immunity and even brain health.

dsm-firmenich is a leading global solutions provider to the Early Life Nutrition and Dietary Supplement industries with a unique portfolio including nutritional lipids, vitamins and custom nutrient premixes. With the integration of HMOs into its portfolio, dsm-firmenich furthers its leadership in providing meaningful solutions to help set infants on a path to a long, healthy life, which is part of our promise to help keep the world’s growing population healthy. Next-generation HMOs are part of dsm-firmenich’s exciting innovation roadmap, with four new HMOs becoming available in the next year to further catalyze the already fast-growing HMO market. 

Recently, dsm-firmenich hosted a webinar focusing on how HMOs impact infant health with world-renowned scientist and physician, Professor Hania Szajewska. Prof. Szajewska summarized how HMO structure affects their function, as well as the current body of evidence related to potential benefits of HMOs in infant nutrition. Click here to watch the recorded webinar.