Human milk oligosaccharides (HMOs), the third most abundant part of human milk, are glycans (sugars), but what is their role? Over the last decade or so, research into the gut and its interactions with HMOs has surged, with lots of positive results. Already these bioactive wonders are displaying so many health benefits, and if the current research to date is anything to go by, this could well be from cradle to grave, and as a bonus, may even push that grave marker a bit further away to boot.
Results from studies have shown HMOs to be instrumental in many physiological processes that take place within the gut and the microbiome. Processes that result in the production of bioactive products that then extend throughout the body. From providing food for the gut bacteria to teaching the immune system how to protect, these little marvels are fascinating.
Intrigued? If so, read on, as in this article we will be investigating another of the HMO family, 3-fucosyllactose, (3’-FL) and all the benefits it has to offer.
What is 3’-FL?
3’-FL is one of the smallest in the HMO family, however, it has been seen in research studies to yield bioactive properties that render this tiny powerhouse simply unique. Naturally present in breast milk from the first stage of lactation, it increases in presence throughout the period, and ultimately it may be small, but not too small to be ignored[i]. This increase is one of the factors that sets it apart from other HMOs and coincides with infants progressing through their early developmental stages.
Although small, 3’-FL is also one of the most abundant HMOs present in human breast milk after 2’-fucosyllactose (2’-FL). Early research has shown that 3’-FL has many benefits for human health, including supporting the growth of good bacteria, promoting a balanced microbiome, and modulating the immune system.
What is the structure of 3’-FL?
Because 3’-FL consists of three sugars, L-fucose, D-galactose and D-glucose, it is a trisaccharide.
Figure 1: Chemical structure of 3’-FL. Source: Christensen et al. (2020)[ii].
3’-FL is technically a constitutional isomer of 2’-FL because it contains the same monosaccharides but with slightly different linkages.
What is the role of 3’-FL?
In comparison to 2’-fucosyllactose, studies into the benefits of 3’-FL have been less abundant (pardon the pun). This said the research that has been conducted has had promising initial findings listing several potential benefits of 3’-FL, such as:
- Being a prebiotic (food) for the gut bacteria
- Aiding the establishment of a balanced gut microbiota
- Assisting brain development and the gut-brain axis in the neonate
- Immunomodulatory properties
- Antimicrobial functions[iii]
3’-FL as a prebiotic and promoting a balanced microbiota
The HMO, 3’-FL, via fermentation, promotes the establishment of a balanced gut microbiota. Its interaction with Bifidobacteria bolsters its colonies to numbers that will maximise health potential as well as keep out potential pathogens.
This balance is essential and will be the springboard from which multiple bioactive reactions will start. The more balanced the gut microbiome is, the greater the health potential[iv]. That’s because a balanced gut is considered vital for health, and because HMOs are largely resistant to the digestive process, they can make it to the gut, feeding the waiting probiotic bacteria. It is this which helps to establish a balanced gut.
The prebiotic properties mean that probiotics, like Bifidobacteria can increase their numbers and their activity, resulting in the increased production of beneficial metabolites, such as short-chain fatty acids (SCFAs)[v].
3’-FL and the production of the short-chain fatty acids
The interactions between 3’-FL and Bifidobacteria lead to a greater production of short-chain fatty acids (SCFAs)[vi].
SCFAs are crucial to gut health, and beyond. For example, they are involved in several integral processes, including:
- Strengthening the integrity of the intestinal barrier. The intestinal barrier has multiple roles, like the uptake of essential nutrients, identifying dangerous potential pathogens via the immune system and blocking them from causing harm[vii].
- Metabolic regulation. Metabolism refers to all the chemical processes in the body. If these processes become disrupted or fail, you are prone to metabolic disorders like, type 2 diabetes and obesity along and the additional effects these conditions bring[viii].
A recent study by Salli et al., (2023) found that the addition of 2’-FL and 3’-FL, either alone or together, increased the abundance of Bifidobacteria species in a colon simulation model and increased the production of SCFAs[ix].
Anti-inflammatory properties
SCFAs also play a major role in combating inflammation. Inflammation can affect many parts of the body with different degrees of seriousness. Inflamed joints can be painful, but chronic inflammation in vital organs, like the heart, liver, and brain can lead to a variety of conditions.
The anti-inflammatory effects that stem from SCFA production via the gut and immune system, can prevent processes that lead to chronic illness, such as the inhibiting chemokines like CXCL10. These chemokines are associated with several infectious diseases, chronic diseases, tumour development, and immune dysfunction, amongst others[x][xi].
Furthermore, 3’-FL has been shown to induce its own anti-inflammatory effects. Kim et al., (2023) demonstrated that 2’-FL and 3’-FL reversed some of the symptoms in DSS-induced acute colitis mice, like body weight loss and short colon lengths. These HMOs also lowered the pro-inflammatory cytokines, interleukin-6 and tumour necrosis factor-α. IL-6 can also disrupt the gut barrier integrity, a major factor in inflammatory bowel disease. Overall, signifying that HMOs can prevent colitis through its anti-inflammatory mechanisms and their ability to strengthen the gut barrier[xii].
3’-FL assisting in brain development
The development of the brain is dependent on a number of factors being in place at the right time and in the right amounts. HMOs like 3’-FL in research studies are believed to promote two of these factors.
- Assisting in shaping the development of the gut microbiota leading to the production of essential metabolites that affect brain function. For example, 3’-FL increased the abundance of Lactobacillus and Bacteroides which are linked to better cognitive outcomes in infants[xiii].
- A source of sialic acid (SA). SA is an integral nutrient of the formation of the myelin sheath around nerves, myelination, this process enables better conductivity. SA is also an essential nutrient in ganglioside formation. Gangliosides negotiate cell-to-cell recognition, signal transduction (external to internal cell signal), and cell-to-cell adhesion[xiv][xv].
A study by Berger et al., (2022) also found that 3’-FL and 3’-SL have important roles in brain development from just 1 month old and are positively associated with fatty acid levels in the growing white matter of the brain.
Gut-brain axis regulation
The gut-brain axis is a pathway of communication, this bidirectional system links or knits the emotional centre with the cognition involving the central and enteric nervous systems.
Having a well-established strong microbiota, the likes of which 3’-FL have been shown to initiate will help shape this remarkable network. Unbalanced microbiota (dysbiosis) has been linked to disorders of the central nervous system like, depression, anxiety, and autism. These conditions are believed to stem from gut disorders such as irritable bowel syndrome (IBS) and irritable bowel disease (IBD) both examples are the result of dysbiosis[xvi][xvii].
More common examples of the power of the gut-brain axis are feelings of nervousness over a particular event or situation, from excitement, and attraction, to stress the brain will send messages that release hormones, and these hormones will tell the digestive system to slow down resulting in a nervous tummy.
3’-FL as an immunomodulator
An immunomodulator, in a nutshell, is a substance that regulates immune responses against a potential illness or disease. If the immune system gets it right, illness and disease can be avoided, but the correct physiological products and information must be in place for the processes to take place.
HMOs like 3’-FL influence these processes, offering protection against microbial infections. Via the manifestation of a good gut microbiota, these protective effects can be exhibited[xviii]. These include
- Cell signalling
- Cell-to-cell event recognition
- Modulation of microbial adhesion, and protection that will stop invasion of the intestinal mucosa
3’-FL and antimicrobial effects
Throughout life we are under constant threat from a whole barrage of potential villainous microorganisms, these can be in the form of:
- Bacteria
- Viruses
- Protozoa[xix]
- Fungi (like mildew or mould spores)
Anti-microbial effects that 3’-FL help to initiate go on to battle against these potential danger-to-life rogues. These anti-microbial agents can not only disrupt their activity they can kill them halting their potential deadly progression[xx][xxi].
A study by Weichert et al., (2013) analysed the biological activity of 2’-FL and 3’-FL in vitro by testing their potential to inhibit pathogen adhesion. 3’-FL stopped the adhesion of enteropathogenic E-coli and Pseudomonas aeruginosa in intestinal cells. Both HMOs also inhibited the adherence of P aeruginosa in human respiratory cells, showing that they can have a potent impact on infectious diseases.
Conclusion
The processes involving 3’-FL are so integral to overall health, that this HMO truly is majestic. From the beginning of life, 3’-FL is busy feeding the gut bacteria and balancing this ecosystem, this then initiates the building of a defence system.
The establishment of a good set of gut microbiota initiates so many processes that help build the complex neuropathways by which every important message will be sent, messages that keep the human body functioning, messages without which disease and chaos would reign, albeit not for long.
The whole kit and caboodle is just truly WOW.
Written by: Leanne Edermaniger, M.Sc.Leanne is a professional science writer who specializes in human health and enjoys writing about all things related to the gut microbiome.
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