HMOs Impact the Gut Microbiome of Children and Adults Starting from Low Predicted Daily Doses
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Updated: Jun 27, 2025

Quantification of the Potential Impact of Glyphosate-Based Products on Microbiomes
Published on: January 10, 2022
Danica Bajic1, Frank Wiens1, Eva Wintergerst1
1DSM Nutritional Products Ltd., Wurmisweg 576, 4303 Kaiseraugst, Switzerland.
Abstract:
Recent studies suggest that the dietary intake of human milk oligosaccharides (HMOs) provides health benefits from infancy up to adulthood. Thus far, beneficial changes in the adult gut microbiome have been observed at oral doses of 5-20 g/day of HMOs. Efficacy of lower doses has rarely been tested. We assessed four HMO molecular species-2'Fucosyllactose (2'FL), Lacto-N-neotetraose (LNnT), 3'Sialyllactose (3'SL), and 6'Sialyllactose (6'SL)-at predicted doses from 0.3 to 5 g/day for 6-year-old children and adults (n = 6 each), using ex vivo SIFR® technology (Cryptobiotix, Ghent, Belgium). This technology employing bioreactor fermentation on fecal samples enables us to investigate microbial fermentation products that are intractable in vivo given their rapid absorption/consumption in the human gut. We found that HMOs significantly increased short-chain fatty acids (SCFAs), acetate, propionate (in children/adults), and butyrate (in adults) from predicted doses of 0.3-0.5 g/day onwards, with stronger effects as dosing increased. The fermentation of 6'SL had the greatest effect on propionate, LNnT most strongly increased butyrate, and 2'FL and 3'SL most strongly increased acetate. An untargeted metabolomic analysis revealed that HMOs enhanced immune-related metabolites beyond SCFAs, such as aromatic lactic acids (indole-3-lactic acid/3-phenyllactic acid) and 2-hydroxyisocaproic acid, as well as 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, for example, the Bifidobacteriaceae family, which had already significantly increased at doses of only 0.5 g/day LNnT (adults) and 1 g/day 2'FL (children/adults).
Insights
Low doses of human milk oligosaccharides (HMOs) significantly benefit the gut microbiome in children and adults. These beneficial changes, including increased short-chain fatty acids (SCFAs), occur at doses as low as 0.3 g/day.
Area of Science:
- Microbiology and Gut Health
- Nutritional Science
- Metabolomics
Background:
- Human milk oligosaccharides (HMOs) are recognized for health benefits extending from infancy to adulthood.
- Previous research established effective adult gut microbiome modulation with 5-20 g/day of HMOs, with lower doses rarely studied.
- Investigating lower HMO doses is crucial for understanding their full therapeutic potential across age groups.
Purpose of the Study:
- To evaluate the efficacy of low dietary doses (0.3-5 g/day) of four specific HMOs (2'FL, LNnT, 3'SL, 6'SL) on the adult and pediatric gut microbiome.
- To identify microbial fermentation products and metabolic changes induced by low-dose HMOs using ex vivo technology.
- To explore the dose-response relationship and specific effects of individual HMOs on gut microbial metabolites.
Main Methods:
- Utilized ex vivo SIFR® technology with bioreactor fermentation on fecal samples from children and adults (n=6 each).
- Assessed four specific HMO molecular species: 2'-Fucosyllactose (2'FL), Lacto-N-neotetraose (LNnT), 3'-Sialyllactose (3'SL), and 6'-Sialyllactose (6'SL).
- Analyzed short-chain fatty acids (SCFAs), untargeted metabolomics, and key microbial populations (e.g., Bifidobacteriaceae).
Main Results:
- HMOs significantly increased SCFAs (acetate, propionate, butyrate) at predicted doses from 0.3-0.5 g/day onwards, with dose-dependent effects.
- Specific HMOs showed distinct impacts: 6'SL on propionate, LNnT on butyrate, and 2'FL/3'SL on acetate.
- Low-dose HMOs enhanced immune-related, gut-brain-axis-related metabolites, and vitamins, and stimulated keystone species like Bifidobacteriaceae at doses as low as 0.5 g/day.
Conclusions:
- Dietary human milk oligosaccharides (HMOs) demonstrate significant beneficial effects on the gut microbiome at considerably lower doses than previously established.
- Low-dose HMOs modulate gut microbial fermentation, producing beneficial SCFAs and other key metabolites, impacting immune function and the gut-brain axis.
- These findings support the potential of low-dose HMO supplementation for promoting gut health in both children and adults.
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