What Are 5 HMO Prebiotics? An In-Depth Look at These Immune-Boosting Sugars

HMOs are the third most abundant solid component in human breast milk, and understanding what are 5 hmo prebiotics can unlock significant health benefits for both infants and adults by supporting gut and immune function. These unique complex carbohydrates are not digested by the human body but instead nourish beneficial bacteria in the colon.

Quick Summary

This article explores five key HMO prebiotics: 2'-FL, LNnT, 3'-SL, 6'-SL, and 3-FL. It explains their mechanisms as nourishment for beneficial gut bacteria and their profound impact on immune function, gut barrier integrity, and potential cognitive development for both infants and adults.

Key Points

• Prebiotic Function: HMOs are not digested by the human body but are selectively fermented by beneficial gut bacteria, primarily Bifidobacterium, acting as a powerful prebiotic.

• Immune Defense: Specific HMOs act as decoys, preventing harmful pathogens and viruses from binding to the intestinal lining and causing infections.

• Gut Barrier Support: HMOs and their fermentation byproducts, like short-chain fatty acids, help strengthen the intestinal barrier, which reduces gut permeability.

• Cognitive Benefits: Sialylated HMOs, such as 3'-SL and 6'-SL, may support brain development by influencing the critical gut-brain axis.

• Adult Health: While found in breast milk, HMOs are also available in supplements and have shown promise in supporting adult gut health, modulating immune responses, and managing conditions like IBS.

• Unique Composition: The complex structure of HMOs, which differs significantly from traditional prebiotics like FOS and GOS, allows for highly specific and targeted health effects.

Human milk oligosaccharides (HMOs) are a complex group of non-digestible carbohydrates found in abundance in human breast milk. While there are over 150 different types, five in particular are frequently highlighted for their significant health benefits. These HMOs act as selective prebiotics, nourishing specific beneficial gut bacteria, particularly Bifidobacterium, and supporting the immune system directly. Modern advancements allow for the bio-identical synthesis of these compounds, making their benefits accessible in infant formulas and adult supplements.

The 5 Key HMO Prebiotics Explained

1. 2'-Fucosyllactose (2'-FL)

As the most abundant HMO in breast milk for most mothers, 2'-FL is also the most extensively studied. It is a fucosylated, neutral trisaccharide composed of L-fucose, D-galactose, and D-glucose. Its primary functions include promoting the growth of beneficial gut bacteria like Bifidobacterium and acting as a decoy to prevent pathogens, such as Campylobacter jejuni, from adhering to the gut lining. By blocking these harmful bacteria, 2'-FL helps protect the body from infections and supports a balanced gut microbiome.

2. Lacto-N-neotetraose (LNnT)

LNnT is another well-researched neutral HMO, often studied alongside 2'-FL. This oligosaccharide is known for its ability to modulate the composition of the gut microbiota. In clinical trials involving infant formula supplemented with both 2'-FL and LNnT, a shift in the infant fecal microbiome was observed, bringing it closer to that of breastfed infants. LNnT helps to create a favorable gut environment for beneficial bacteria to flourish, supporting digestive wellness.

3. 3-Fucosyllactose (3-FL)

Distinct from 2'-FL due to a different glycosidic linkage, 3-FL also serves as a prebiotic, contributing to the diversity of the gut microbiome. Research indicates that different fucosylation patterns can have unique impacts on specific pathogens. While both 2'-FL and 3-FL are fucosylated, they may affect the growth of different bacteria or inhibit different pathogens, showcasing the varied functions of individual HMOs.

4. 3'-Sialyllactose (3'-SL)

3'-SL is a sialylated HMO, containing sialic acid—a crucial component for brain and cognitive development. Studies suggest that 3'-SL may influence the gut-brain axis, potentially supporting learning and memory. Furthermore, acidic HMOs like 3'-SL have shown anti-adhesive properties against specific uropathogenic strains of E. coli, among other pathogens.

5. 6'-Sialyllactose (6'-SL)

Similar to 3'-SL, 6'-SL is another sialylated HMO containing sialic acid. It plays an important role in immune system support and brain development. Both 3'-SL and 6'-SL contribute to cognitive function by influencing the gut-brain axis, demonstrating the multifaceted benefits of HMOs beyond just gut health. A mixture of 3'-SL and 6'-SL has also been shown to be effective against certain rotavirus infections.

How HMO Prebiotics Differ from Traditional Prebiotics

Traditional prebiotics, such as inulin, fructo-oligosaccharides (FOS), and galacto-oligosaccharides (GOS), are often based on repeating sugar units. They provide general nourishment for a wide range of gut bacteria. In contrast, HMOs possess a much more complex structure, containing additional functional groups like N-acetylglucosamine, fucose, and sialic acid. This structural complexity allows HMOs to offer more targeted and specific health benefits. Unlike traditional prebiotics, HMOs are known to uniquely nourish Bifidobacterium longum infantis, and their specific linkages are crucial for defense mechanisms and immune functions. Furthermore, HMOs can act as decoys, directly preventing pathogens from binding to the gut wall, a mechanism not observed in traditional prebiotics.

The Health Benefits of Individual HMOs: A Comparison

HMO Type	Primary Function	Unique Structural Component	Key Health Benefits
2'-FL	Promotes Bifidobacterium growth	Fucose linkage	Blocks pathogen adhesion, supports immune system
LNnT	Modulates gut microbiota composition	Type-2 chain elongation	Creates a favorable gut environment
3-FL	Supports microbial diversity	Different fucose linkage	Unique anti-pathogen effects depending on the pathogen
3'-SL	Influences gut-brain axis	Sialic acid	Supports cognitive development, fights specific pathogens
6'-SL	Supports immune/brain axis	Sialic acid	Aids brain development, enhances immune response

The Role of HMOs Beyond Infancy

While first experienced by infants, research shows that adults can also benefit significantly from HMO supplementation. In adulthood, HMOs can help reverse gut dysbiosis and repair the intestinal barrier, often referred to as leaky gut. This strengthens the gut lining by promoting the production of tight junction proteins. Studies on adult gut microbiota have demonstrated that supplementation with a mix of 2'-FL and LNnT can beneficially modulate the microbial community. Furthermore, HMOs can reduce gut inflammation and may help alleviate symptoms associated with inflammatory diseases like IBS. The fermentation of HMOs by bacteria also produces short-chain fatty acids (SCFAs), which are vital for maintaining gut health and providing energy to colon cells.

How to Get More HMOs

For infants, the primary source of HMOs is human breast milk, but many infant formulas now include bio-identical HMOs like 2'-FL and LNnT to replicate some of breast milk's benefits. For adults, HMOs are available in dietary supplement form, often as powders or capsules. A product guide from Layer Origin Nutrition details their SuperHMO® Prebiotic Mix with 5 HMOs, including 2'-FL, 3'-SL, 6'-SL, LNT, and LNnT. When considering supplementation, it is always recommended to consult a healthcare professional to determine appropriate dosages and suitability for your specific health needs.

Conclusion

The complex family of human milk oligosaccharides (HMOs) includes several key prebiotic powerhouses that extend benefits far beyond infancy. The five HMO prebiotics, including 2'-FL, LNnT, 3-FL, 3'-SL, and 6'-SL, each contribute unique functions to support the gut microbiome, strengthen the immune system, and promote neurological development. Their structural complexity and selective feeding patterns differentiate them from traditional prebiotics, offering more targeted benefits. For both infants and adults, incorporating these specific HMOs, either through fortified formulas or targeted supplements, can be a highly effective strategy for fostering digestive and immune wellness and may provide significant long-term health advantages. Further research continues to uncover the full potential of these remarkable compounds in maintaining health throughout the lifespan.

References

• Šuligoj, T., Vigsnæs, L. K., Abbeele, P. V. D., et al. (2020). "Effects of Human Milk Oligosaccharides on the Adult Gut Microbiota and Barrier Function." Nutrients, 12(9), 2808. https://doi.org/10.3390/nu12092808
• Wiciński, M., Sawicka, E., Gębalski, J., et al. (2020). "Human Milk Oligosaccharides: Health Benefits, Potential Applications in Infant Formulas, and Pharmacology." Nutrients, 12(1), 266. https://doi.org/10.3390/nu12010266
• Walsh, C., Lane, J. A., van Sinderen, D., & Hickey, R. M. (2020). "Human milk oligosaccharides: Shaping the infant gut microbiota and supporting health." Journal of Functional Foods, 72, 104074. https://doi.org/10.1016/j.jff.2020.104074
• Laucirica, I. C., et al. (2023). "Prebiotics in New-Born and Children's Health." Microorganisms, 11(10), 2453. https://doi.org/10.3390/microorganisms11102453

Frequently Asked Questions

Are all human milk oligosaccharides (HMOs) the same?

No, over 150 different types of HMOs have been identified in human breast milk. They vary in size, structure, and composition, leading to different biological functions and targeted effects within the gut microbiome.

Can adults take HMOs, or are they only for infants?

While HMOs are a natural component of breast milk for infants, they are also available as supplements for adults. Research has shown that adult supplementation can help modulate gut microbiota, improve gut barrier function, and support immune health.

How do HMOs protect against infections?

HMOs can protect against infections in a unique way by acting as decoy receptors. They mimic the cell-surface structures that pathogens use to bind, preventing harmful bacteria and viruses from attaching to the intestinal wall and allowing them to be flushed from the body.

What is the difference between HMOs and probiotics?

HMOs are prebiotics, meaning they are a food source for beneficial bacteria. Probiotics are the live, beneficial bacteria themselves. HMOs selectively nourish specific good bacteria, like Bifidobacterium, helping them to thrive.

Is there a difference in benefit between 2'-FL and LNnT?

Yes, while both are beneficial prebiotics, they have different chemical structures and metabolic properties. 2'-FL is a fucosylated HMO, whereas LNnT is a neutral, non-fucosylated type. They work synergistically to support the gut, but research shows they have distinct influences on the microbiome.

Can a person's diet affect the HMO composition in breast milk?

While maternal genetics play a significant role in determining HMO composition (e.g., secretor status), research suggests that factors like diet, stage of lactation, and ethnicity can also influence the concentration and types of HMOs.

Do all infant formulas contain HMOs?

No, not all infant formulas contain HMOs. However, many major brands now fortify their formulas with specific HMOs, such as 2'-FL and LNnT, to replicate some of the functional benefits of breast milk.

How do HMOs contribute to brain development?

Some HMOs, particularly sialylated ones like 3'-SL and 6'-SL, contain sialic acid, which is a key nutrient for cognitive function. These HMOs are believed to influence the gut-brain axis, supporting neurological development.