December 13, 2022 13 min read
Arriving on the planet as a neonate, be it by the birthing canal or by caesarean section (C Section), you are confronted with a whole wealth of potential dangers. There are obvious environmental factors and conditions, but just as threatening are those that are lurking within. Fortunately, there are forces at work that, if unfolded correctly, will see the neonate receive an internal shield of protection, this being the gut microbiota that lines the gastrointestinal tract (GI tract).
The gut microbiota is a collective term relating to all the different species and strains of bacteria that inhabit our GI tract. Billions of tiny organisms are essential to our survival. Our first meeting with them is as we journey from our mother into the big, open world. Here we are, in effect, swabbed with a good dousing of microbes from mum, a sort of bacterial baptism.
The first bacteria we encounter are Bifidobacteria and Lactobacilli, which are important and termed good bacteria. The abundance of the bacteria we encounter can depend on the levels within our mother. For example, if our mother had recently completed a course of antibiotics, she, under normal circumstances, could be in a state of dysbiosis, where bacteria levels are out of balance. In this case, we could receive low amounts of good bacteria[i].
Another situation where the neonate could be left with an altered abundance or composition of bacteria is if they are delivered by C-section. They will not encounter these important bacteria because they do not pass through the birthing canal or the vagina[ii].
But there is a backup plan, all ready and waiting, to either reinforce the bacteria we have already received from our successful natural birth or to strengthen a poor initiation of bacteria we have received due to complications or circumstances. This backup plan comes from human milk, or what is first scientifically called colostrum. But we’re particularly interested in a specific component of human breast milk called human milk oligosaccharides (HMOs). These are the third most abundant part of our mother’s breast milk.
HMOs are cool things because they have multiple benefits for us and our gut bacteria. There is lots of scientific research stating just how valuable HMOs are for our health from being infants into childhood and beyond[iii]. The contact between our early gut inhabitants and the nutrients our mother can supply is deemed so important that infant formula milk is now being fortified with HMOs[iv][v].
However, these same HMOs that provided so much support when we arrived are now seen as pivotal and instrumental in repairing our adult gut microbiota. That’s because HMOs for adults have the power to reverse gut dysbiosis, prevent disease, and repair damage[vi].
Please read on as we delve deep into the world of our gut microbiome and its interaction with HMOs, what they are, how they work, and why they are so important for our continued health, even in adulthood.
People ask, ‘are human milk oligosaccharides carbohydrates?’ The answer is yes. HMOs are the sugar part of your mother’s milk. They belong to a group of complex carbohydrate molecules called glycans, an amazing, structurally diverse group[vii]. They are thought to have several direct and indirect roles that support human health. These include:
HMOs are prebiotics because they are a food source for specific beneficial gut bacteria. HMOs provide the sustenance bacteria need to become abundant and help to achieve a balanced microbiome. As well as this, the process also generates short-chain fatty acids (SCFAs), a bi-product of bacterial fermentation that are also crucial for both gut and general health. The production of SCFAs assists in regulating metabolism, inflammation, and disease.
Although HMOs are a major component of human breast milk and an important part of a breastfed infant’s diet, emerging research shows they can also have striking results in adults.
The results of the health benefits of HMOs in adults are relatively young as far as the research goes, with most studies conducted in the last few decades. Yet, the research has been largely very promising. More than 200 types of HMOs have been identified so far, highlighting just how diverse these active components are. There are two HMOs which are of particular interest when it comes to adult health; they are 2’-fucosyllactose (2’FL) and lacto-N-neotetraose (LNnT).
Both have been featured in many scientific studies to observe their potential in disease prevention, symptom reversal in some illnesses and diseases and anti-inflammatory reversing qualities.
Some illnesses human milk oligosaccharides for adults may be beneficial for include:
Let’s look closer at the potential health benefits of HMOs for adults.
In babies, HMOs stimulate the growth of Bifidobacteria. These HMO prebiotic benefits are seen in adults, too, alongside HMOs’ ability to modulate the immune system, benefit brain health and regulate the gut barrier.
Bifidobacteriaare a type of bacteria that thrive in environments with little oxygen and are natural inhabitants of the human gut. The human body is not equipped with the enzymes it needs to break down indigestible carbohydrates like fibre, so our gut bacteria do it for us via a process called fermentation.
When bacteria like Bifidobacteria break down these foods, they transform them into magic molecules the body can use, such as short-chain fatty acids and vitamins. Other bacterial species can use these metabolic bi-products to help them grow and thrive, resulting in a diverse gut microbiome that is key for good health. The ability of bacteria to feed other species is called cross-feeding and, in this case, helps to increase the abundance of butyrate producers.
It’s not just about keeping other microbes satisfied; cross-feeding also has immunity benefits because it keeps inflammation low and supports good gut health. The best way to boost your Bifidobacterialevels is through HMO supplementation.
That’s because HMOs, like Layer Origin HMO Super Prebiotic Powder, are exclusively selective for Bifidobacteria, unlike other prebiotic supplements that simultaneously feed other bacterial species.
The lining of the gut is not entirely impenetrable. It can’t be, otherwise, how could good stuff like nutrients enter the rest of our body? However, like most things in life, it is possible to have too much of a good thing, and a highly penetrable gut is one of them. Often referred to as a leaky gut.
Your gut lining acts like security for the rest of your body; it allows some components access (nutrients) and denies entry to others (toxins, pathogenic bacteria, and undigested food). This intestinal permeability plays a major role in our health. However, if the gut barrier becomes impaired or compromised, it can lead to toxins entering the body, inflammation and an increased risk of chronic disease[viii].
The overall composition of the gut microbiome can affect the intestinal barrier through the regulation of tight junction proteins (the gatekeepers). Generally, an imbalance in the gut microbiota can lead to an impaired gut barrier, contributing to an increased risk of gut diseases such as irritable bowel disease (IBD). For this reason, it is essential to find solutions to this increasing problem, and because of their well-documented effects on the human gut microbiota, HMOs could be vital.
For example, a study by Suligoj et al. (2020) investigated what effect HMOs had on the adult human gut using a Simulator of the Human Intestinal Microbial Ecosystem (SHIME), Caco2 cell lines, and human intestinal gut organoid-on-chip. The HMOs studied were a 4:1 mix of 2’FL & LNnT, equivalent to 10g per day.
The results showed that by using the supplement, fermentation led to an increased abundance of Bifidobacteriaand an increase in short-chain fatty acid production, especially butyrate, in response to 2’FL. The study concluded that HMOs could beneficially modulate the gut barrier by reducing permeability and increasing tight junction proteins. These results strengthen the case that HMOs can provide health benefits, mainly through restoring or promoting gut barrier function in adultsvi.
The gut-brain axis is a unique and complex way in which the body has 2-way lines of communication between the gut and the central nervous system (CNS). This axis is believed to be influenced and regulated by gut microbiota composition[ix].
The dynamic changes that take place alter the metabolite profiles within the gut. At the same time, this changes the biomolecules that directly influence the function and health of the brain. Pretty clever stuff, right? It’s also why you’ll sometimes hear the gut referred to as the body’s second brain.
The powerful effect that these changes within gut microbiota have also interact and initiate changes to the endocrine, neurological, and immunologic pathways that form the microbiota-gut brain-axisviii.
Animal studies, for example, have demonstrated that giving a human milk oligosaccharide supplement either alone or in combination can have long, lasting and beneficial effects on cognition and memory[x].
As we’ve seen, HMOs are an important player regarding the gut-brain axis. Using irritable bowel syndrome (IBS) as an example, IBS is signified by several symptoms, all of which are associated with the gut, such as:
However, a leading cause of this condition is stress, which has many knock-on effects, ranging from effects on the nervous system, structural changes to the brain, chronic disease and even death[xi].
A study by Iribarren et al. (2021) of 58 male and female patients aged 18 – 75 years and all suffering from IBS, with symptoms ranging from moderate to severe, studied the effects of HMOs on IBS symptoms.
The study stated that IBS could be a gut-brain axis disorder due to the displayed psychological symptoms. It noted that the microenvironment of the intestine could be a major player in its development.
It used past and growing evidence to suggest that the host microbiota’s activity impacts the host immune response and intestinal epithelial cells, which then could regulate mucosal barrier functions. Interventions to modulate and improve the host microbiota crosstalk with the epithelial cells could contribute to the management of IBS symptoms.
The study was a phase II, parallel, double-blind, randomised, placebo-controlled study. And used a 4:1 mix of 2’FL HMO supplement and LNnT HMO supplement, respectively. After screening, the patients were divided into three groups, placebo, 5g mix of the supplement or 10g mix of the supplement.
The mix was administered daily for four weeks, with faecal, mucosal, and colon biopsy samples taken at baseline and four weeks. The participants also completed a questionnaire at the beginning and end of the intervention relating to the severity of pain, anxiety, and depression scale.
From the faecal sample and the colonic mucosal biopsies, the microbiota composition was analysed using 16s rDNA sequencing. Using Horizontal bead beating, the samples were briefly disrupted using a Vortex Genie 2. This was performed at 2700 rpm for five minutes, and then total bacterial DNA was isolated. Further tests what performed for a polymerase chain reaction and rDNA primers using sequencing from which an assignment of species-level, specifically Bifidobacteriumstrains, was attempted.
The 58 patients received were split into the following groups, placebo = 19, 5g = 20, and 10g = 19. The effects of 2’FL and LNnT on gut microbiota diversity and richness were investigated. Operational Taxonomic Units were used to determine the species richness of both faecal and mucosal samples. These were found to be comparable in all groups at baseline. However, the 4-week samples showed the 10g mix group having a higher microbiota composition than the placebo group. No differences were seen in the mucosal microbiota between the groups.
The study summarised that the 4-week supplementation intervention using 2’FL/LNnT had shaped the gut microbiota in the IBS patients. A more visible increase was seen in the faecal and mucosal strains of B. adolescentisand mucosal B. longum.
There was also modulation of the faecal and plasma metabolite profiles, but the host mucosal responses were not seen to be influenced throughout the intervention.
Throughout the intervention, a metabolite modulation linked to bifidogenic effect was seen, and the overall findings found that using the supplementation of 2’FL and LNnT could well be of value to improve the microbiota in IBS patients, but further tests should be undertaken to assess the further potential beneficial effects on the IBS patient[xii].
Earlier studies, such as West et al. (2016), have also shown that beneficial bacteria can reverse stress-induced gut dysmotility[xiii].
In infants, HMOs affect the immune system through various mechanisms. They can even regulate the immune response, meaning they play a crucial role in developing immunity.
Emerging research has identified that HMOs can interact with the immune system and prevent some genes from synthesising inflammatory cytokines. In other words, HMOs could dampen down inflammation and may also help to relieve some of the symptoms of autoimmune conditions.
For example, He et al. (2014) found that a mix of HMOs could alter T cell-mediated cytokine production, resulting in immune tolerance. This is particularly important in developing autoimmune conditions, which are associated with an increased level of cytokines in the circulation[xiv].
But HMOs can also help to build protection by other means too, including:
The HMOs directly affect how the host's epithelial immune response is modulated towards pathogenic bacteria and viruses. This modulation can selectively make binding to the gut epithelium a no go for both the pathogenic bacteria and the viruses, thus preventing disease[xi]. Often this happens because HMOs look similar to the cell surface structures pathogenic bacteria have called glycans. So, HMOs can bind to the host’s surface instead, preventing the pathogen from attaching and excreting them from the body without causing harm.
HMOs can modulate the gut microbiome's composition and promote Bifidobacteria's growth. This is important because a healthy gut microbiome is one where Bifidobacteriausually dominates.
So, how does this help with our immune function?
Viruses are a significant threat to our health. Although some vaccines are available to protect us against some viral pathogens, viruses can evolve, making it difficult to produce effective vaccines.
However, HMOs could have the potential to protect against some viral pathogens, such as:
No, HMOs are prebiotics because they are a naturally occurring compound that helps to feed beneficial bacteria, stimulating their growth and activity. Probiotics, on the other hand, are live bacteria or yeasts that can have health benefits if consumed in large enough quantities.
Yes, 2-FL is a type of HMO and is, therefore, a prebiotic.
Glycans are a type of bioactive molecule present in human milk as human milk oligosaccharides (HMOs), conjugated lipids, or proteins. You may see HMOs described as milk glycans.
HMO supplements are an excellent way to boost your Bifidobacterialevels and reap the benefits of doing so. HMO supplements support gut health and immunity. Layer Origin Nutrition has a wide range of HMO and related supplements, like Layer Origin apple peel powder, to help promote health.
Although from we birth appear to be under threat of invasion that ultimately could take us out of the game, there had already been a predisposed element of, ‘yeah you try it, we’ve got this kid covered’ with an army of tiny microorganisms reinforced by mighty human milk oligosaccharides poised ready to defend us. Then as we move towards adulthood, it may have seemed that we were on our own.
Unfortunately, maybe for many centuries we just may have got a bit lost in our understanding. But there was no abandonment. As the many studies and trials are showing, the assistance has always been there, assistance to carry us with a continued shield, not complete immunity, but a helping hand none the less.
Our own internal microbial world, assisted by mighty HMOs, help us to get it right, and all we need to do, is do right by them, could it be any easier?
As the research continues who knows where it could lead, but for now we can take comfort in the fact that modern science is opening doors that are shining a big light on how we can improve our health and make our time on this planet a little easier.
And that is it for this article, hopefully it has highlighted just how important it is that we get the balance of our own tiny mighty inner world right, and of course, get back on them HMOs.
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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[v] Vandenplas Y, Berger B, Carnielli VP, Ksiazyk J, Lagström H, Sanchez Luna M, Migacheva N, Mosselmans JM, Picaud JC, Possner M, Singhal A, Wabitsch M. Human Milk Oligosaccharides: 2'-Fucosyllactose (2'-FL) and Lacto-N-Neotetraose (LNnT) in Infant Formula. Nutrients. 2018 Aug 24;10(9):1161. doi: 10.3390/nu10091161. PMID: 30149573; PMCID: PMC6164445.
[vi] Šuligoj T, Vigsnæs LK, Abbeele PVD, Apostolou A, Karalis K, Savva GM, McConnell B, Juge N. Effects of Human Milk Oligosaccharides on the Adult Gut Microbiota and Barrier Function. Nutrients. 2020 Sep 13;12(9):2808. doi: 10.3390/nu12092808. PMID: 32933181; PMCID: PMC7551690.
[vii] Heinrich V, Lee CY. Blurred line between chemotactic chase and phagocytic consumption: an immunophysical single-cell perspective. J Cell Sci. 2011 Sep 15;124(Pt 18):3041-51. doi: 10.1242/jcs.086413. PMID: 21914817; PMCID: PMC3172184.
[viii] Marcelo Campos MD. Leaky gut: What is it, and what does it mean for you? [Internet]. Harvard Health. 2021 [cited 2022Dec11]. Available from: https://www.health.harvard.edu/blog/leaky-gut-what-is-it-and-what-does-it-mean-for-you-2017092212451
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[xi] Walsh C, Lane JA, van Sinderen D, Hickey RM. Human milk oligosaccharides: Shaping the infant gut microbiota and supporting health. J Funct Foods. 2020 Sep; 72:104074. doi: 10.1016/j.jff.2020.104074. Epub 2020 Jul 3. PMID: 32834834; PMCID: PMC7332462.
[xii]Iribarren C, Magnusson MK, Vigsnæs LK, Aziz I, Amundsen ID, Šuligoj T, Juge N, Patel P, Sapnara M, Johnsen L, Sørensen N, Sundin J, Törnblom H, Simrén M, Öhman L. The Effects of Human Milk Oligosaccharides on Gut Microbiota, Metabolite Profiles and Host Mucosal Response in Patients with Irritable Bowel Syndrome. Nutrients. 2021 Oct 27;13(11):3836. doi: 10.3390/nu13113836. PMID: 34836092; PMCID: PMC8622683.
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