HMOs impact the gut microbiome of children and adults starting from low predicted daily doses
Introduction
So far, beneficial impact of HMOs on the adult gut microbiome has been observed at oral doses of 5-20 g/day of HMOs. However, the efficacy of lower doses has rarely been tested.
Objective
New research highlights the significant health advantages of human milk oligosaccharides (HMOs) from childhood through adulthood. While previous studies focused on higher doses, this study examined the effects of lower HMO doses on both children and adults.
Method
We assessed four HMO molecular species, 2’Fucosyllactose (2’FL), Lacto-N-neotetraose (LNnT), 3’Sialyllactose (3’SL) and 6’Sialyllactose (6’SL), with doses ranging from equivalents of 0.3 to 5 g/day for 6-years-old children, and adults (n = 6 each), using the ex vivo SIFR® technology. This technology employing bioreactor fermentation of fecal samples enables investigation of microbial fermentation products that are intractable in vivo given their rapid absorption/consumption in the human gut. We assessed the effect of HMOs on microbiota composition (via quantitative shotgun sequencing) and metabolic activity (via gas chromatography for SCFA, and untargeted metabolomics).
Results
We found HMOs to significantly increase acetate, propionate (children/adults) and butyrate (adults) from predicted doses of 0.3-0.5 g/day onwards, with stronger effects as dosing increased. Untargeted metabolomic analysis revealed for both groups that HMOs enhanced immune-related metabolites like aromatic lactic acids (indole-3-lactic acid/3-phenyllactic acid) and 2-hydroxyisocaproic acid, gut-brain axis-related metabolites (γ-aminobutyric acid/3-hydroxybutyric acid/acetylcholine) and vitamins. The effects of low doses of HMOs potentially originate from the highly specific stimulation of keystone species belonging to, amongst others, the Bifidobacteriaceae family that already increased significantly at only 0.5 g/day LNnT (adults) and 1 g/day 2’FL (children/adults).
Conclusion
The key finding of the study is that in vitro HMOs significantly impact health-associated microbial taxa and related metabolites from doses that are well below those commonly applied in clinical studies involving adults (5–20 g/day). Significant HMO-dependent, dose-dependent, and age-dependent effects were noted for many metabolites. This research not only underscores the importance of low doses of HMOs in promoting gut health but also suggests their therapeutic potential across different age groups. These findings offer new avenues for enhancing overall well-being from childhood to adulthood.