The Rise of HMOs: Advancing Infant Nutrition Through Science
What Are HMOs and Why Do They Matter?
Human Milk Oligosaccharides (HMOs) are the third most abundant solid component in breast milk—following lipids and lactose—and even outnumber proteins. These complex, non-digestible carbohydrates are made up of three to thirty sugar units, crafted from five core monosaccharides: galactose, glucose, N-acetyl glucosamine, N-acetyl neuraminic acid, and fucose.
With over 200 known structures, HMOs are grouped into three primary types:
- Fucosylated HMOs (contain fucose)
- Sialylated HMOs (contain sialic acid)
- Neutral HMOs (made from galactose, glucose, and acetylglucosamine)
Function & Impact
HMOs aren’t just nutritional fillers—they play key roles in:
- Gut health: Acting as prebiotics, nourishing beneficial gut bacteria
- Immune protection: Serving as decoys to block viruses and pathogens from binding to the intestinal wall
- Brain development: Especially those with sialic acid, which may aid neurological growth
HMOs in Infant Formula: The Current Landscape
Mimicking the natural composition of human milk is a gold standard in formula design—but it’s not without challenges. In human milk:
- The top 10 HMOs can make up 70% of the total HMO profile
- The most dominant HMO might represent up to 30% alone
However, replicating these structures in formula is costly. That’s why many infant formulas rely on prebiotic substitutes like:
- Galacto-oligosaccharides (GOS)
- Fructo-oligosaccharides (FOS)
- Polydextrose
Advances in HMO manufacturing are reducing production costs and paving the way for broader inclusion of real HMOs—starting with the most prevalent and scaling up.
Testing Technology: Precision in HMO Detection
The current testing method hinges on derivatizing HMOs with 2-aminobenzamide, tagging them with a fluorescent marker for selective and sensitive analysis. These are then separated by Hydrophilic Interaction Chromatography (HILIC) and detected via fluorescence.
Seven significant HMOs are highlighted through this testing process, which include:
- 2'-Fucosyllactose
- 3-Fucosyllactose
- 3'-Sialyllactose
- 6'-Sialyllactose
- Lacto-N-tetraose
- Lacto-N-neotetraose
- Difucosyllactose
This approach minimizes interference and allows accurate quantification—even in complex formula blends.
Method Development & Industry Validation
Originally approved as a First Action Method in 2022, this testing technique has undergone further refinement:
- A second method using ultra-high-performance liquid chromatography (UHPLC) offered increased resolution and expanded coverage
- Rather than choosing one over the other, experts merged both methodologies for a comprehensive solution
The merged method received First Action status and is slated for multi-lab validation, enabling an optimized method for analysis across a wide variety of formulas.
Looking Ahead: Scaling Innovation
Until large-scale HMO production becomes more accessible, manufacturers will continue using prebiotic alternatives. However, clinical research is rapidly identifying which HMOs offer the greatest health benefits—informing future formulation strategies.
With deeper insights into HMO behavior and enhanced column technologies, analytical teams are already positioned to adapt to new structures as they emerge.
Bottom Line
The use of real HMOs in infant formula is accelerating, driven by science, innovation, and a commitment to nourishing infants in the healthiest way possible. Enhanced testing methods are unlocking new capabilities—bringing us closer than ever to replicating the complexity and power of human milk.
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