Human milk oligosaccharides (HMOs) are complex sugar molecules found abundantly in human breast milk. These carbohydrates are the third most plentiful solid constituent after lactose and fat, playing a distinct role in infant development.
Understanding Human Milk Oligosaccharides
HMOs are carbohydrates that infants do not digest directly for nutrition. These molecules travel largely intact through the infant’s digestive system to the colon. They are synthesized within the mammary gland from five different monosaccharides: β-d-galactose, β-d-glucose, β-d-N-acetylglucosamine, α-l-fucose, and α-d-N-acetylneuraminic acid (sialic acid). This process creates over 150 HMO structures.
HMOs are present in concentrations ranging from 5 to 15 grams per liter in mature milk, and up to 20 grams per liter in colostrum, the first milk produced after birth. They are classified into neutral non-fucosylated (42–55%), neutral fucosylated (35–50%), and sialylated (12–14%) categories. Their species-specificity highlights their functions for infants.
How HMOs Benefit Infant Health
HMOs benefit infant development by interacting with the gut microbiome and immune system. They function as prebiotics, selectively feeding Bifidobacterium, a dominant microbe in breastfed infants’ intestines, which supports a healthy gut environment. Bifidobacterium longum subspecies infantis is especially adept at utilizing HMOs, leading to the production of short-chain fatty acids like acetate, propionate, and butyrate.
HMOs exhibit anti-adhesive and antimicrobial properties, acting as “decoy receptors” that prevent pathogens from attaching to the infant’s gut surfaces. By mimicking binding sites on gut cells, HMOs can bind directly to bacteria and viruses, hindering their colonization. This mechanism helps protect against various infections, including those caused by Escherichia coli and Streptococcus agalactiae.
HMOs modulate the infant’s immune system. They interact directly with immune cells, including neutrophils, macrophages, and T-cells, influencing their activation and cytokine production. This interaction regulates inflammatory responses and supports the maturation of innate and adaptive immunity. For example, certain HMOs can competitively inhibit the activation of Toll-like receptor 4 (TLR4), reducing inflammation and promoting immune balance.
Emerging research suggests a role for HMOs in brain development and cognitive function. Studies have linked higher concentrations of specific HMOs, such as 2′-fucosyllactose (2′-FL) and 6′-sialyllactose (6′-SL), in breast milk to improved cognitive and motor skills scores in infants. Sialic acid, a component of some HMOs, is a building block for gangliosides in the brain and supports synapse formation and neurotransmission. HMOs influence the gut-brain axis, a communication pathway between the gut and the central nervous system.
HMOs in Infant Formula
Historically, infant formulas lacked the oligosaccharides found in human milk. The production of HMOs for commercial use faced challenges due to their intricate structures and difficulty in isolation or synthesis. However, advancements in biotechnology have made it possible to synthesize specific HMOs, allowing their inclusion in infant formulas.
The first commercially available HMO, 2′-fucosyllactose (2′-FL), was launched in 2015, followed by the inclusion of both 2′-FL and Lacto-N-neotetraose (LNnT) in some infant formulas by 2018. These synthesized HMOs are structurally identical to those found naturally in human milk. Fortifying formula with HMOs aims to replicate some benefits of breast milk, particularly in shaping a healthy gut microbiome and supporting immune function. While these additions narrow the compositional gap, natural human milk contains over 200 diverse HMO structures, which is still more complex than current formula compositions.
Emerging Research and Future Applications
Research into HMOs continues to expand beyond their established benefits for infants. Scientists are exploring their roles in adult health, particularly in the gut microbiome and immune system. Studies indicate that HMOs can influence the adult gut microbiota, promoting the growth of Bifidobacterium strains and increasing the production of short-chain fatty acids at doses ranging from 0.3 to 20 grams per day.
Preliminary studies suggest that specific HMOs, such as 2′-FL, may reduce intestinal inflammation and promote gut barrier integrity in adult models of inflammatory conditions. These findings suggest HMOs as therapeutic agents for immune-related conditions and gut-brain axis disorders, including inflammatory bowel disease. While promising, these adult applications are still under investigation and require further clinical research.