It takes guts and science: Unlock the latest research behind human milk oligosaccharides (HMOs) for human health

Summary

• Supplements featuring human milk oligosaccharides (HMOs) hold significant promise for infant and adult nutrition, offering benefits for digestive health, immunity and brain function.
• To keep gut health innovators informed in this rapidly evolving and emerging field of research, we’ve summarized key findings from two new papers exploring the impact of HMOs on the gut microbiome and immune response.
• Read on to decode the latest HMO science and stay one step ahead of evidence-based claims in the health and nutrition space.

In recent years, consumer interest in gut health has grown exponentially. This is largely due to increased public understanding and awareness of the gut microbiome and its influence on overall health. Additionally, gastrointestinal issues and food sensitivities are on the rise, making protecting gut health a priority for many.^1,2 With this comes interest in innovative gut-supporting ingredients, including one next-generation prebiotic supplement that is taking the gut health market by storm – human milk oligosaccharides (HMOs).

HMOs are a group of carbohydrates that are abundant in human breast milk, the gold standard for infant nutrition. They play an important role in the health and development of infants, namely feeding important beneficial bacteria in the gut, which in turn supports the development of a robust immune system and protects against harmful microbes.³ In infants, HMO supplementation has been shown to modulate both immune cells and pathogens directly – delivering benefits before even reaching the microbes in the gut.³ Additionally, they may support brain and cognitive development through the gut-brain-axis.⁴

New preclinical and clinical research reveals that the benefits of HMOs can be leveraged throughout life to nourish, protect and reinforce the gut microbiota of children and even adults.^5,6,7 Read on to discover key findings from two papers published this year by dsm-firmenich researchers investigating the influence of HMOs on the gut microbiome and human immune cells specifically.

1. The impact of low dose HMOs on gut microbiota 

Previous studies have examined the benefits of HMOs in children and adults at high doses (5 – 20 g/day).^5,6 These doses have been shown to be safe and tolerated in adults, however the European Food Safety Authority (EFSA) recommends much lower doses for children.⁸ A new study published in Metabolites this year used a cutting-edge ex vivo system (SIFR® technology) to examine the effects of four HMOs (2′-fucosyllactose (2′-FL), lacto-N-neotetraose (LNnT), 3′Sialyllactose (3′SL) and 6′Sialyllactose (6′SL)) at low doses on microbiota and microbial metabolism from human samples.9 The HMOs were applied at doses between 0.3 – 5g/day and the microbiota of six children and six adults were examined – with both groups seeing benefits of HMOs at these lower amounts.

Firstly, the growth of beneficial bacterial species was enhanced with HMO treatment. For example, all four HMOs markedly increased the abundance of Bifidobacteria species in the microbiota of children, especially 2’FL which showed this effect from doses of 1 g/day. In the microbiota of adults, 2’FL and LNnT both significantly increased levels of the Bifidobacteria species at low doses, with doses of LNnT as low as 0.5 g/day showing a significant effect. Furthermore, 6’SL (and 3’SL to a lesser extent) boosted Bacteroides species in both children and adults (at 5 g/day for both). These results are important because many species from the Bifidobacteria and Bacteroides genera are important components of a healthy gut microbiome in humans of all ages, and some can also act as ‘keystone’ species, which are important for the establishment of healthy microbiomes.⁹

The HMOs were also associated with significant increases in the production of beneficial short-chain fatty acids (SCFAs) – metabolites important for maintaining gut health and supporting immune regulation.^10,11 All four HMOs increased levels of all SCFAs in a dose-dependent manner, however there were differences in the degree of effect depending on the HMO ingredient. For example, acetate was primarily increased by 2’FL and 3’SL, whereas propionate was most markedly increased by 6’SL. In the case of butyrate, the effects of HMOs were much more pronounced in adults (mostly by LNnT), which aligns with the fact that butyrate producing species are enriched in more mature gut microbiota. Other metabolites increased with HMO treatment included aromatic lactic acids and neurotransmitters like acetylcholine, which are related to immunity and the gut-brain axis respectively, as well as B vitamins.⁹

In summary, the study revealed that HMOs can support gut microbiota and provide health benefits for both adults and children, even at lower doses. Furthermore, the research indicates which HMO ingredients may be better suited to different life stages and that specific health benefits can be addressed with certain HMOs. This could serve as an important guide for supplement formulation in the Health from the Gut and Early Life Nutrition markets.

2. HMOs help to prepare white blood cells to fight infection

HMOs have previously been shown to influence immune cells, however the specific effects of different structures on human macrophages (an important type of white blood cell from the innate immune system) have yet to be fully defined. A new study featured in Frontiers of Immunology examined the impact of three individual HMOs, 2’FL, LNnT and 6’SL, on macrophages responding to infection with the pathogen Staphylococcus aureus (also known as S. aureus).¹²

The study found that macrophages treated with HMOs, particularly 6’SL, showed increased expression of genes, surface markers and cytokines related to M1 macrophage activation when exposed to S. aureus. This M1-response is important in defense against S. aureus infection and is associated with pathogen clearance and illness recovery. The results of the study further confirmed that 6’SL enhanced macrophage phagocytosis (a process where macrophages engulf and remove pathogens) of S. aureus. Importantly, the HMOs did not trigger unnecessary activation of immune cells in the absence of the pathogen.

To sum up, the results of this research illustrated that HMOs, specifically 6’SL, enhance the ability of macrophages to respond effectively to S. aureus infection, but do not activate an inflammatory response in macrophages in the absence of pathogen – and therefore essentially ‘prime’ the macrophages to fight infection. This demonstrates the importance of HMOs in infant nutrition and the potential for use of HMOs in children and adults infected with S. aureus – and possibly other pathogens in the future.

3. Conclusions and opportunities to innovate 

In these studies, HMOs demonstrate effects at low doses and influence the ability of immune cells to respond to pathogens. Notably, the data shows that different HMOs have different biological effects. These findings can be used to direct further preclinical and clinical research, as well as to guide the formulation of Health from the Gut and Early Life Nutrition supplements. For example, nutritional solutions featuring HMOs could be targeted to different age groups or to address specific health benefits.

As a pioneer in this space, we remain at the forefront of cutting-edge HMO research. Our continued investment has informed the development of our advanced HMO portfolio, the broadest commercially-available offering worldwide – and led to many exciting discoveries in this field of science.