HMOs Definition
Human Milk Oligosaccharides (HMOs) are complex, non-digestible carbohydrates found in high concentrations in human breast milk. Representing the third most abundant solid component after lactose and lipids, HMOs are key to shaping the neonatal microbiota, modulating immune responses, and providing passive protection against pathogens. As research on HMOs expands, so does the demand for advanced synthesis and structural analysis solutions. At Creative Biolabs, we're proud to support global HMO research with custom oligosaccharide synthesis and comprehensive oligosaccharide analytical services, tailored to help you unlock the bioactive potential of these remarkable glycans.
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Natural HMOs
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Synthetic HMOs
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Source
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Human breast milk
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Industrial fermentation or enzymatic synthesis
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Structural Diversity
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Over 200 distinct structures
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Limited to a few major types (e.g., 2′-FL, LNnT)
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Bioactivity
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Comprehensive health benefits
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Comparable benefits, but may lack some minor components
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Production Variability
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Influenced by maternal genetics and lactation stage
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Controlled and consistent production processes
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Cost and Accessibility
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Naturally occurring, limited availability
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Widely accessible via fortified formulas or supplements
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HMOs Structure
HMOs are composed of five key monosaccharides: glucose, galactose, N-acetylglucosamine, fucose, and sialic acid. Based on charge and sugar composition, they fall into three major structural classes:
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Neutral HMOs: These include structures such as Lacto-N-tetraose (LNT) and Lacto-N-neotetraose (LNnT), which account for approximately 35% to 50% of the total HMOs.
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Acidic HMOs: These contain sialic acid residues, imparting a negative charge. Notable examples include 2′-Fucosyllactose (2′-FL), 3′-Sialyllactose (3′-SL), and 6′-Sialyllactose (6′-SL), collectively comprising about 12% to 14% of total HMOs.
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Non-glucuronic Acid Neutral HMOs: These lack both sialic acid and glucuronic acid units, representing approximately 42% to 55% of the total HMOs.
Representative HMO Structures
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HMO Type
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Structure Description
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LNT
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Lactose core + N-acetyllactosamine
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LNnT
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Similar to LNT with alternate linkages
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2′-FL
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Lactose + α1-2 linked fucose
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3′-SL
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Lactose + α2-3 linked sialic acid
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6′-SL
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Lactose + α2-6 linked sialic acid
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Fig.1 Structures of Representative HMOs.1
These diverse glycosidic linkages and terminal motifs are directly linked to HMO bioactivities. For instance, 2′-FL fosters Bifidobacterium longum growth while mimicking epithelial receptors to block pathogen adhesion. In contrast, 2′-FL supports neurodevelopment and attenuates inflammation by donating sialic acid for ganglioside biosynthesis.
HMOs Functions
Immune Modulation
HMOs interact with innate immune cells like dendritic cells and macrophages, modulating cytokine profiles. Studies show that HMOs such as 2′-FL and 3-FL can balance Th1/Th2 responses, reducing allergen-induced inflammation.
Prebiotic Effects & Pathogen Suppression
As highly selective prebiotics, HMOs are metabolized by Bifidobacterium and Lactobacillus species. They also competitively inhibit adhesion of pathogens such as E. coli and Group B Streptococcus (GBS). Notably, elevated HMO levels in breast milk correlate with reduced HIV transmission during lactation.
HMOs Antiviral and Antibacterial Applications
Pathogen Adhesion Blockade and Barrier Enhancement
HMOs stop infections by imitating epithelial surface glycan receptors. These substances decrease GBS vaginal colonization and biofilm formation in murine models which results in reduced preterm birth risk. HMOs prevent norovirus from binding because they compete with the natural host receptors. HMOs increase tight junction expression which strengthens the intestinal barrier to protect against microbial translocation and systemic inflammation.
Inflammatory Pathway Suppression
HMOs prevent the activation of the NF-κB signaling pathway which helps reduce persistent inflammation associated with IBD, asthma and allergic diseases. Supplementing the diet of OVA-sensitized mice with 2′-FL and 3-FL led to lower IgE and mMCP-1 levels while also strengthening epithelial integrity. 2′-FL modified the intestinal bacterial environment and decreased inflammatory cytokines within colitis models which indicates potential therapeutic uses.
HMOs Research Methods
Advancing HMO Synthesis
Technological advancements have enabled efficient microbial production of HMOs using gene-modified strains of Bacillus subtilis or engineered yeast. These platforms yield structurally defined HMOs like 2′-FL with high purity and scalability. At this stage, selecting the right partner for HMO-related R&D can make a critical difference.
HMOs Analysis Methods and Technologies
Accurate analysis of HMOs is essential for research and quality control. The primary analytical techniques used in HMO research are as follow, these analytical methods at Creative Biolabs provide comprehensive tools for the qualitative and quantitative analysis of HMOs, facilitating advancements in understanding their structures and functions.
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Technique
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Applications
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High-Performance Liquid Chromatography (HPLC)
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Quantification and purification of individual HMOs.
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Mass Spectrometry (MS)
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Structural elucidation and quantification of HMOs.
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Nuclear Magnetic Resonance (NMR) Spectroscopy
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Detailed structural analysis of HMOs, including linkage positions and configurations.
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Capillary Electrophoresis (CE)
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Analysis of HMO mixtures with high resolution and speed.
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Lectin Microarrays
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Profiling of HMO interactions with proteins and assessment of glycan-binding specificities.
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Matrix-Assisted Laser Desorption/Ionization-Time of Flight Mass Spectrometry (MALDI-TOF MS)
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Rapid identification and characterization of HMOs and their derivatives.
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Our Custom Oligosaccharide Services
From synthesis to structural analysis, Creative Biolabs offers end-to-end support tailored to your project's goals—whether you're optimizing biosynthetic pathways, analyzing glycan-protein interactions, or designing functional HMO analogs.
Creative Biolabs leads in custom oligosaccharide synthesis and analysis services to help your HMO research progress from initial idea to clinical application. Our scientific expertise combined with advanced platforms and a dedication to client needs establishes us as the preferred partner for precision glycoscience. Contact us now so we can turn your oligosaccharide objectives into realities.
FAQs
Q: Why are human milk oligosaccharides important?
A: Human milk oligosaccharides (HMOs) act as prebiotics, selectively promoting the growth of beneficial bacteria, and help establish a healthy intestinal environment critical for nutrient absorption and immune tolerance. Moreover, HMOs prevent infections by mimicking host cell surface glycans, thus acting as decoy receptors for pathogens including E. coli, Campylobacter, and Norovirus. Emerging evidence also suggests roles in neurodevelopment, reduction of inflammation, and protection against allergic diseases, highlighting their value not only in nutrition but also in therapeutic applications.
Q: Are synthetic HMOs as good as natural ones?
A: Synthetic HMOs like 2′-FL closely replicate natural structures and offer comparable health benefits, including gut and immune support. However, natural breast milk contains over 200 HMO types, so mimicking the full spectrum may require combining multiple synthetic HMOs to fully match natural functionality.
Reference
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Garádi, Zsófia, et al. "Utilizing the 1H-15N NMR methods for the characterization of isomeric human milk oligosaccharides." International Journal of Molecular Sciences 24.3 (2023): 2180. Distributed under Open Access license CC BY 4.0, without modification. https://doi.org/10.3390/ijms24032180
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