The HMO research history spans more than a century of scientific breakthroughs, taking us from a simple observation about infant health to cutting-edge biotechnology that’s transforming nutrition for both babies and adults. This fascinating journey reveals how scientists gradually uncovered nature’s hidden formula for nourishing newborns—and how that discovery is now opening doors to healthy aging for all of us.
The Early Days: When Breastfeeding Wasn’t Considered Important
It may surprise you to learn that around 1900, breastfeeding wasn’t considered particularly important by the medical community. Infant mortality rates were alarmingly high, and pediatricians were desperately searching for answers.
Two pivotal observations changed everything. First, French biochemist Georges Denigés noticed in the late 19th century that human milk and cow’s milk contained different carbohydrate structures beyond simple lactose. Meanwhile, pediatricians Ernst Moro in Austria and Henry Tissier in France independently observed something remarkable: the fecal composition of breastfed infants differed dramatically from bottle-fed babies.
Tissier’s 1900 discovery of Lactobacillus bifidus (later reclassified as Bifidobacterium) in breastfed infants proved to be a major milestone. He found that breastfed babies had intestinal bacteria dominated by these beneficial microbes, while formula-fed infants lacked this protective flora. This observation led to a critical question: what exactly in breast milk was feeding these beneficial bacteria?
The 1930s: Gynolactose—The First Clue
Around 1930, French scientists André Polonowski and Lina Lespagnol identified a mysterious milk carbohydrate fraction they called “gynolactose.” This marked the official starting point of human milk oligosaccharide research, though scientists at the time didn’t yet understand its true significance.
For nearly two decades, gynolactose remained an enigma. Researchers knew it was present in human milk but absent or minimal in cow’s milk, yet they couldn’t explain why or what it did.
The 1950s Breakthrough: Kuhn and György Solve the Puzzle
The breakthrough came when two brilliant scientists from different disciplines joined forces. In 1926, researcher Schönfeld had reported that human milk whey contained a growth-promoting factor for Lactobacillus bifidus, but the chemical nature of this “bifidus factor” remained unknown.
Enter chemist Richard Kuhn in Germany and pediatrician Paul György in Philadelphia. These two had previously collaborated in Heidelberg three decades earlier on vitamin research. When they reconnected in the 1950s, they hypothesized a connection between Moro and Tissier’s bacterial observations and Polonowski’s gynolactose.
Their collaboration proved spectacularly successful. By the mid-1950s, Kuhn and György confirmed that the bifidus factor consisted of oligosaccharides containing N-acetylglucosamine and polysaccharides. They had finally identified what made breast milk so uniquely beneficial for infant gut health.
Even more remarkably, their work revealed that influenza virus cleaves specific oligosaccharide structures in human milk, explaining breast milk’s antiviral properties. This discovery had lasting influence across chemistry, biology, and medicine.
1960s-1980s: Mapping the HMO Universe
Following this breakthrough, researchers embarked on an intensive effort to characterize individual HMOs. French scientist Jean Montreuil, a pioneer in carbohydrate chemistry, made crucial contributions by proposing that all N-glycans share the same core structure with various mobile “antennae” branches.
During these three decades, scientists discovered that human milk oligosaccharides represent the third most abundant solid component in breast milk after lactose and lipids, present at concentrations of 20-25 g/L in colostrum and 5-20 g/L in mature milk. They identified approximately 200 different HMO structures—an astounding diversity that highlighted nature’s sophisticated approach to infant nutrition.
Researchers discovered that HMOs include both neutral and acidic (sialylated) structures. Among the sialylated oligosaccharides, 3′-sialyllactose (3′-SL) and 6′-sialyllactose (6′-SL) emerged as particularly important, accounting for 10-30% of total HMOs—a concentration roughly 100-fold higher than in cow’s milk.
The Manufacturing Challenge: From Milk to Fermentation
For decades, HMO research was hampered by a critical limitation: scientists could only obtain small quantities of HMOs by laboriously isolating them from donated human milk. This severely restricted research possibilities and made commercial applications impossible.
Between 2005-2012, Danish company Glycom A/S pioneered large-scale chemical synthesis of 2′-fucosyllactose (2′-FL) and lacto-N-neotetraose (LNnT). However, chemical synthesis proved complex, expensive, and unsuitable for mass production.
The real game-changer came in 2000 when Japanese firm Kyowa Hakko Bio became the first company to establish an industrial-scale HMO production system using precision fermentation. By engineering microorganisms like E. coli and yeast to produce HMOs through fermentation—similar to how vitamins are made—scientists could finally create structurally identical HMOs in commercial quantities at accessible prices.
2015-2020s: The Commercial Revolution
The breakthrough in manufacturing technology sparked a regulatory and commercial revolution. In September 2015, the U.S. FDA granted the first regulatory approvals for chemically synthesized 2′-FL and LNnT, followed by approvals for fermentation-derived versions in November 2016.
Major infant formula manufacturers rapidly incorporated HMOs into their products. Abbott launched Similac Pro-Advance with 2′-FL HMO in 2016, and clinical studies showed that formula-fed babies receiving 2′-FL had immune system markers nearly identical to breastfed infants.
The innovation accelerated dramatically. By 2021, Abbott introduced Similac 360 Total Care containing five different HMOs—2′-FL, 3-FL, LNT, 3′-SL, and 6′-SL—representing all major structural classes found in breast milk. European approval of HMOs as novel foods opened markets worldwide, and China’s regulatory approval in recent years positioned HMOs to reach millions more infants.
The global HMO market has exploded, projected to grow from $275 million in 2025 to nearly $880 million by 2032, with compound annual growth rates of 18-20%.
Beyond Infant Nutrition: HMOs for Adults
Here’s where the story takes an exciting turn for adults. Recent research reveals that HMOs aren’t just for babies. Scientists discovered that individual HMOs like 6′-sialyllactose can help prevent muscle atrophy and support healthy aging, while 3′-sialyllactose strengthens the intestinal barrier and promotes digestive wellness.
Research published in 2024 demonstrated that 6′-SL prevents dexamethasone-induced muscle atrophy by controlling protein degradation pathways. A pilot clinical trial showed that 6′-SL improved limb muscle power in adult patients with GNE myopathy. Meanwhile, studies on 3′-SL revealed its ability to enhance tight junction proteins, promote epithelial renewal, boost short-chain fatty acid production, and reduce intestinal inflammation.
These findings have opened an entirely new frontier for HMO applications. What started as infant nutrition research has evolved into a promising avenue for supporting muscle health, digestive function, and healthy aging in adults.
Looking Forward: The Next Chapter
After more than a century of research, HMO science continues to accelerate. Advanced fermentation technologies, new analytical methods, and expanding clinical evidence are revealing even more applications for these remarkable molecules. Researchers are now investigating HMOs’ roles in brain development, immune modulation, and protection against various health challenges.
The evolution from chemistry to biotechnology has made what was once exclusively available to breastfed babies now accessible to formula-fed infants—and increasingly, to health-conscious adults seeking to optimize their wellbeing as they age.
That’s why Siallac® was developed—to bring the science-backed benefits of specific sialylated oligosaccharides to adults. Siallac® Muscle Health harnesses 6′-sialyllactose to support strength and resilience as we age, while Siallac® Gut Health utilizes 3′-sialyllactose to help maintain a healthy digestive system. These products represent the latest chapter in the remarkable HMO research history, translating over 100 years of scientific discovery into practical solutions for adult health.
References
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- Go, H., Sung, N.J., Choi, J., Kim, L., & Park, E.J. (2024). 6′-sialyllactose prevents dexamethasone-induced muscle atrophy by controlling the muscle protein degradation pathway. Biochemical and Biophysical Research Communications. https://doi.org/10.1016/j.bbrc.2024.150892
- Wang, B., McVeagh, P., Petocz, P., & Brand-Miller, J. (2003). Brain ganglioside and glycoprotein sialic acid in breastfed compared with formula-fed infants. American Journal of Clinical Nutrition, 78(5), 1024-1029. https://doi.org/10.1093/ajcn/78.5.1024
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- Sprenger, N., et al. (2022). Biology of human milk oligosaccharides: From basic science to clinical evidence. Journal of Human Nutrition and Dietetics, 35(2), 280-299. https://doi.org/10.1111/jhn.12990
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