Human milk oligosaccharides

Human Milk Oligosaccharides (HMOs)

Around 1900, scientists discovered that human breast milk contains complex carbohydrates distinct from lactose, later referred to as milk carbohydrates. Early research suggested that these components contributed significantly to the improved survival rates of breastfed infants. At that time, breastfed infants were approximately seven times less likely to die than infants fed animal milk or mixtures of milk with cereals, and occasionally meat or pre-chewed foods. Importantly, breastfeeding was not widely recognized as a critical factor for infant health during this period (Kunz 2012).

Further observations revealed that these milk carbohydrates selectively stimulated the growth of beneficial microorganisms in the infant gut. These bacteria were initially called Lactobacillus bifidus, now known as bifidobacteria. The carbohydrates responsible for this effect are now known as human milk oligosaccharides (HMOs).

HMOs are the most abundant non-digestible bioactive components in human milk after lactose and lipids. To date, over 200 structurally distinct HMOs have been identified, each with specific biological functions. Unlike nutrients that directly feed the infant, HMOs primarily act by shaping the infant’s gut environment and immune development.

Biological Functions of HMOs 

Since their discovery, extensive research has demonstrated that HMOs exert multiple beneficial effects, far beyond their original classification as prebiotics (DSM 2022).

1. Prebiotic effects

HMOs selectively nourish beneficial gut bacteria, particularly Bifidobacterium species. This promotes the development of a healthy infant microbiome and leads to the production of short-chain fatty acids (SCFAs), which:

• Provide energy to colon cells
• Lower intestinal pH
• Inhibit the growth of pathogenic microorganisms

2. Anti-pathogen activity

HMOs function as soluble decoy receptors, mimicking cell-surface glycans on the intestinal lining. Pathogenic bacteria and viruses bind to HMOs instead of the gut epithelium and are subsequently excreted, reducing the risk of gastrointestinal and respiratory infections.

3. Immune system programming

HMOs play a critical role in immune maturation by:

• Promoting immune tolerance
• Modulating inflammatory responses
• Reducing the risk of allergies, asthma, and autoimmune conditions

4. Gut barrier integrity

HMOs strengthen intestinal tight junctions, enhancing gut barrier function and reducing intestinal permeability. This protective effect helps prevent systemic inflammation and microbial translocation.

5. Neurodevelopment and the gut–brain axis

Emerging evidence suggests that HMOs may support neurological and cognitive development, potentially via microbiota-mediated signaling along the gut–brain axis and through the provision of sialic acid, a key component in brain development.

Consequences of limited or absent HMO exposure 

Given the importance of HMOs in early-life development, limited or absent exposure to breast milk and HMOs may be associated with an increased risk of:

• Chronic low-grade inflammation
• Autoimmune diseases
• Allergic conditions and atopy
• Gut dysbiosis
• Impaired immune regulation

While infant formula has improved substantially, it historically lacked these complex bioactive components.

Bio-identical HMOs and modern applications 

Advances in precision fermentation now allow for the production of bio-identical HMOs, also referred to as human-identical milk oligosaccharides (HiMOs). These compounds are structurally identical to those found in human milk.

Today, selected HMOs are added to infant formulas to more closely replicate the functional benefits of breast milk. In addition, HMOs have entered the adult nutrition and supplement market for their beneficial effects on gut health.

The first user experiences and research look very promising. People report significant improvements in gut dysbiosis related symptoms, leading to an increased quality of life.