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The gut, also known as the second brain, has a direct hotline to the brain called the gut-brain axis. This unique bi-directional communication pathway links the gut microbiota with the central nervous system (CNS) and can directly influence brain function and health. Secondary to this, human milk oligosaccharides (HMOs) are important prebiotics that can modulate the composition of the gut microbiome which could influence the activity and function of the brain.
The human gut-brain axis is an important two-way communication pathway between the brain and the gut. These two important organs are connected not only physically but also by several other means[i], including via:
The gut and brain are so intrinsically linked that changes in the gut microbiota can contribute to health conditions that manifest outside of the gastrointestinal tract, including Alzheimer’s Disease[ii] and Parkinson’s Disease[iii]. Therefore, highlighting that the gut and its inhabitants are a promising therapeutic target for treating disease both inside and outside the gut, especially as the gut microbiota participates in the production and regulation of several neuroactive biomolecules that can impact brain health and function via the gut-brain axis. In other words, the microbiota is integral to the health of your brain.
Mind-blowing isn’t it?
Figure 1.The gut microbiome and the brain are connected via the gut-brain axis, a bi-directional communication pathway that’s controlled by various systems, including the immune, nervous, and circulatory systems. Changes in the gut microbiota composition or activity have been linked to neurodegenerative diseases, mood disorders, and autism spectrum disorder[iv]. (Source: Loh et al (2024))
The gut microbiota is a diverse community of microbes, predominantly bacteria whose composition can be influenced by several factors, including:
When healthy, the gut microbiome retains a mutually beneficial relationship with its human host, but if it becomes imbalanced, also known as dysbiosis, it can increase the risk of disease in both the gut and beyond.
Much research has been conducted into the health benefits and effects of the gut microbiome and it has been shown to have important roles in:
Animal studies have also shown that the gut microbiota can influence the production of certain biomolecules that influence the brain, including serotonin. Wikoff and Colleagues (2008) showed that blood levels of serotonin were increased 2.8 fold in conventional mice compared to germ-free mice, suggesting a significant role of the gut microbial community in the production of blood metabolites[v].
So, where do HMOs come in?
Human milk oligosaccharides are the third most abundant component of human breast milk and have a significant role in shaping the early gut microbiota and immune system in infants. Because HMOs are resistant to enzymes and acidic conditions, they can pass freely through the digestive tract to reach the colon intact. Here, specific gut bacteria use them, predominantly Bifidobacteria, to enable them to thrive and survive.
However, HMOs can also indirectly influence the intestinal environments. For example, they can inhibit the colonization of pathogens, interact with the immune system, and bolster the epithelial barrier, all of which can keep dysbiosis at bay. Many studies have shown that HMOs are safe and well-tolerated by adults and that they may also influence cognitive development in infants[vi]. Therefore, this indicates that HMOs potentially have much broader health benefits than those that are only confined to the gut, including via the central nervous system.
Figure 2.HMOs can influence the composition of the gut microbiome in infants, children, and adults. Through their ability to induce shifts in the gut, they could also affect the brain in several ways, such as through the production of neuroactive molecules, like SCFAs and neurotransmitters, the vagus nerve, or by an as yet undefined pathway[vii]. (Source: Al-Khafaji et al (2020))
Here we explore the potential role of HMOs in the development of CNS disorders and their impact on the gut-brain axis.
HMOs can modulate the composition of the gut microbiota, particularly through their ability to increase the growth and activity of Bifidobacteria, important members of the intestinal ecosystem. That’s because they are important SCFA producers, especially acetate and lactate, which go on to nourish butyrate producers, such as Faecalibacterium prausnitzii,through the process of cross-feeding[viii].
The composition of the gut microbiome has been implicated in several chronic diseases affecting the brain and cognition. For example, in autism spectrum disorder (ASD) children were seen to have lower abundances of health-promoting species such as Akkermansia, Bifidobacteria, and Bacteroides, and higher concentrations of Faecalibacterium[ix]. Similar studies have shown a decreased abundance of butyrate producers in people with depression[x].
Similarly, a study by Keshavarzian et al (2015) found that the gut microbiota composition in Parkinson’s Disease patients was significantly different from control patients. They found that butyrate producers were more abundant in controls while pro-inflammatory Proteobacteria were significantly abundant in Parkinson’s Disease patients. Therefore, noting that proinflammatory dysbiosis was present in Parkinson’s Disease and could contribute to its development[xi].
In contrast, HMOs are known to stimulate the growth and activity of butyrate producers via Bifidobacteria which Al-Khafaji and Co. (2020) have speculated could be advantageous in Parkinson’s Disease. Likewise, Guo et al (2023) showed that daily administration of sodium butyrate in Parkinson’s Disease induced mice resulted in:
Therefore, by initiating the increased production of important health-promoting short-chain fatty acids, HMOs could be a useful tool for the treatment, management, and maybe even prevention of CNS disorders.
Gamma-aminobutyric acid (GABA) is a chemical messenger or neurotransmitter in your brain. It’s an inhibitory neurotransmitter because it can slow your brain down and produce a calming effect. GABA is also critical in the gut-brain axis, not least because certain species of Bifidobacterium and Lactobacillus contain the genes responsible for its biosynthesis and transport. These microbes convert monosodium glutamate into GABA in the gut via the enzyme glutamate decarboxylase[xiii].
GABA participates in the production of neurotransmitters like dopamine and serotonin. If this pathway becomes dysfunctional it could contribute to the development of cognitive impairments and stress-related conditions. So, it is possible that if the gut microbiome becomes imbalanced and there is a low abundance of probiotic bacteria, this could result in a decrease in GABA in the gut which could relate to a GABA reduction in the CNS.
HMOs could potentially increase the production of GABA, through their microbiome-modulating capabilities.
Figure 3.How HMOs could impact the production and regulation of neuroactive molecules as hypothesised by Al Khafaji et al (2020).
Figure 3 demonstrates how HMOs could be involved in the production and regulation of certain neuroactive molecules, as stated by Al Khafaji and Co.
Research shows that breastfed infants have greater cognitive development compared to formula-fed infants[xiv]. Some of this could be due to the HMO content with further studies showing that they can have beneficial effects on memory and cognition[xv].
2’-Fucosyllactose (2’-FL) is the most commonly used HMO and has been studied for its potential effects on cognition in recent years. Some of the research has concluded that 2’FL:
More nuanced research is demonstrating some more potential effects of HMOs on brain health.
The most common sialylated HMOs are 3’-siallylactose (3’SL) and 6’-sialylactose (6’-SL). They are important in neurodevelopment. In piglets, administering a protein-bound source of sialic acid was shown to enhance learning and development. Therefore, this suggests that sialic acid in milk could be important for cognitive development[xix].
Oliveros et al (2018) found that 6’SL increased cognitive outcomes, improving memory and long-term potentiation in rats[xx].
Did you know?You can capitalise on the benefits of 3’SL and 6’SL with our SuperHMO® Prebiotic Mix with 5 HMOs.
At Layer Origin, we recently conducted our own research into the impact of our PureHMO® products on specific symptoms our consumers may be experiencing. Although it is no surprise that the majority of our customers expected to see results relating to their gut and digestion, cognitive benefits were also found.
Figure 4.The results from our consumer survey found that brain fog severity scores fell by 32.5% following supplementation with our PureHMO products.
Brain fog is not a medical term but is a collection of symptoms that can affect:
As previous research has alluded to, HMOs can have benefits for memory and cognition in animal models, even at a mature age. Therefore, our research helps to back up the claim that HMOs might have a positive impact on the health and function of the brain.
If you’re looking to support the health of your gut and potentially harness the power of PureHMO®, get yours here.
Manipulating and modulating the composition of the gut microbiome could have potential benefits for brain health and function. Specifically, HMOs could be key to this because they can reach the gut intact and be used by probiotic bacteria species. In turn, HMOs directly and indirectly influence the gut-brain axis and could offer therapeutic options for CNS disorders. Further research is needed to fully understand the mechanisms that HMOs adopt to influence brain health but their influence is promising.
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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