Human Milk Oligosaccharides and Infant Gut Microbiota

Human milk oligosaccharides (HMOs) constitute the third most abundant solid component of breast milk, comprising a remarkably diverse array of complex carbohydrates. Although indigestible by the infant’s own enzymes, these structures traverse the upper gastrointestinal tract intact and reach the colon, where they act as selective substrates for beneficial bacteria. In particular, HMOs foster the proliferation of bifidobacteria, shaping a microbial community that reinforces the mucosal barrier, deters pathogen adherence, and modulates immune development. Variability in HMO composition is driven by maternal genetics—principally the fucosyltransferase‐dependent secretor and Lewis phenotypes—and is further influenced by physiological factors such as lactation stage, parity and environmental conditions. Through direct and indirect mechanisms, HMOs contribute to the maturation of gut architecture, refinement of immune responses and establishment of a health‐promoting microbial ecosystem during a critical window of infant development.

Research from Nature Portfolio

Efforts to expand access to HMOs have turned to novel bioengineering platforms. Transgenic plants capable of synthesising a spectrum of structurally distinct HMOs—including complex fucosylated and sialylated species—have been demonstrated to support robust bifidobacteria growth in vitro and exhibit prebiotic efficacy comparable to native human milk. Technoeconomic analyses project that plant‐based production could offer a sustainable, cost‐effective route to large‐scale HMO manufacture, overcoming limitations of microbial fermentation. In parallel, longitudinal monitoring of HMO profiles from a large European cohort has elucidated the temporal trajectories of over twenty individual oligosaccharides during the first four months postpartum. This work confirms that lactation stage and milk group genotype remain the primary determinants of HMO variation, while maternal body mass index, mode of delivery and parity contribute modestly to concentration differences. Together, these studies chart both the supply and compositional dynamics of HMOs, informing strategies to replicate the functional complexity of human milk.

Human Milk Oligosaccharides and Infant Gut Microbiota publication trend

The graph below shows the total number of articles in human milk oligosaccharides and infant gut microbiota across all publications each year (not limited to Nature Index journals).

Technical terms

Human milk oligosaccharides (HMOs): Complex glycans unique to human milk that resist digestion and serve as selective substrates for beneficial gut bacteria.

Secretor status: A genetic trait determined by fucosyltransferase enzymes that governs the presence of specific fucosylated HMOs in breast milk.

Prebiotic: A substrate that is selectively utilised by host microorganisms conferring health benefits to the host.

Bifidobacterium: A genus of anaerobic bacteria commonly enriched by HMOs, associated with positive gut and immune development in infants.

References

1. Engineered plants provide a photosynthetic platform for the production of diverse human milk oligosaccharides. Nature Food (2024).
2. Human milk oligosaccharides, antimicrobial drugs, and the gut microbiota of term neonates: observations from the KOALA birth cohort study. Gut Microbes (2023).
3. Human milk oligosaccharide composition is affected by season and parity and associates with infant gut microbiota in a birth mode dependent manner in a Finnish birth cohort. EBioMedicine (2024).
4. Immunological Effects of Human Milk Oligosaccharides. Frontiers in Pediatrics (2018).
5. Physiology of Consumption of Human Milk Oligosaccharides by Infant Gut-associated Bifidobacteria*. Journal of Biological Chemistry (2011).
6. Campylobacter jejuni Binds Intestinal H(O) Antigen (Fucα1, 2Galβ1, 4GlcNAc), and Fucosyloligosaccharides of Human Milk Inhibit Its Binding and Infection*. Journal of Biological Chemistry (2003).
7. Impact of maternal characteristics on human milk oligosaccharide composition over the first 4 months of lactation in a cohort of healthy European mothers. Scientific Reports (2019).