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.