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Prebiotics for the Mind and Psyche – Building the Foundations of the Gut-Brain Axis

AUTHOR: Andrija Karačić, M.D., specializing in abdominal surgery and the founder of the Gut Microbiome Center in Zagreb

It seems that probiotics are the "big brother" of prebiotics, and therefore, they have captured all the attention of the scientific and professional community. But are prebiotics really three times less important?

No, prebiotics are not probiotics. Although their names differ by only one vowel, pro- and prebiotics are quite different. Probiotics are microorganisms that are definitely the stars of the story about the gut microbiome. When we search the PubMed database of scientific papers, under the term “probiotics,” it will offer us as many as 45,427 publications. For comparison, if we do this for the term “prebiotics,” it offers us only 14,764 publications – three times less. Probiotics seem to be the big brother of prebiotics, who has picked up all the attention of the scientific and professional community. But are prebiotics really three times less important?”

Prebiotics, in layman’s terms, are ‘food for good bacteria.’ This applies to both the probiotics we ingest from the outside and the bacteria deeply embedded in the intestinal biofilm, which we’ve discovered through genome sequencing over the last decade. The key aspect of prebiotics is that they are indigestible and reach the intestinal microbiome untouched by our digestive juices. However, their most important feature is their selective use by only certain members of the same intestinal microbiome.

While numerous chemical substances reach our intestinal microbiome, prebiotics are utilized by those bacteria that will promote our organism’s well-being for their growth and development. Traditionally, these have been bacteria from the genera Lactobacillus and Bifidobacterium, which is why prebiotics are also called bifidogenic. Anaerobic fermentation of prebiotics leads not only to the growth of ‘good’ bacteria but also to the production of metabolites that, through their action on the intestinal barrier, immunity, metabolism, and nervous system, result in numerous positive health effects when prebiotics are consumed. This means that prebiotics not only alter the composition but also the metabolism or functionality of the intestinal microbiome.

For many years, fibres were primarily considered as prebiotics, a heterogeneous group of plant-derived carbohydrate polymers. However, due to advancements in gut microbiome research, the range of prebiotics is expanding day by day. It has been established that unsaturated fatty acids and polyphenols also possess prebiotic potential. It’s expected that with new insights into bacterial metabolism, there will be discoveries of new groups of chemical substances with prebiotic properties, such as peptides and proteins.

Although not as popular as probiotics, prebiotics indeed represent an intriguing scientific field. This is evidenced by the fact that a review article from 2016 included prebiotics in the so-called psychobiotics. But what exactly are psychobiotics?

The term ‘psychobiotics‘ was coined by Professor John Cryan and Ted Dinan, scientists from the University of Cork in Ireland, a leading global institution in gut-brain axis research. Observing a significant body of research pointing to the psychotropic effects of probiotics, psychobiotics were defined as microorganisms with positive impacts on mental health. Today, prebiotics are also considered psychobiotics because, due to their influence on the composition and functionality of the gut microbiome, they alter the functioning of the gut-brain axis, yielding beneficial effects on the mind and psyche. How do prebiotics alter the gut-brain axis?

The gut-brain axis refers to a theoretical model that encompasses all forms of interaction between the gut and the brain. The key mediator in this interaction is the gut microbiome, primarily due to its immense metabolic potential in producing metabolites with immunomodulatory, neuroactive, and metabolic effects. The presence and activity of gut bacteria can indirectly influence, among other things, mood, cognition, and memory. Studies even suggest that human behaviour is significantly influenced by the gut microbiome. The fact that we don’t understand how the brain functions without the influence of the gut microbiome speaks volumes about the impact of the gut-brain interaction on brain function.

To better comprehend the action of prebiotics on the gut-brain axis, it’s important to understand what the gut microbiome requires for this axis to function properly. The most crucial factor is balance, specifically a balance between major taxonomic groups (phyla, genera) and anti-inflammatory and potentially pathogenic bacteria that stimulate an inflammatory response. While we are not able to precisely define a healthy gut microbiome, numerous studies conclude that it primarily needs to be balanced. A balanced gut microbiome functions as an ecosystem aiding in digestion and defending against invasive pathogenic microorganisms. Diversity is the foundation of balance. The greater the number of diverse taxonomic and functional groups, the more robust and stable the ecosystem becomes.

Although we often categorize bacteria as ‘good’ or ‘bad,’ all bacteria play a role in the microbial ecosystem when their numbers are in balance with others. Each additional bacterial gene present in the gut microbiome contributes to its overall genetic potential, subsequently reflecting its metabolic potential. Thus, a balanced and diverse composition of the gut microbiome is closely linked to its functionality.

Dysbiosis refers to the imbalance within the gut microbiome, whether in taxonomic or functional groups. Although dysbiosis as a condition is not precisely defined, the mechanism by which it leads to health issues and disrupts the gut-brain axis is known. For instance, if certain microorganisms dominate, it can lead to excessive breakdown of the mucous layer of the intestinal lining. The loss of the protective function of the gut barrier opens pathways for toxins and even bacteria to enter the systemic circulation and eventually reach the central nervous system. This condition, popularly known as ‘leaky gut,’ is associated with the development of a pro-inflammatory response in the body at a systemic level. This occurs due to an exaggerated activation of the immune system aimed at eliminating toxins and pathogenic microorganisms. This pro-inflammatory response, within the central nervous system, is linked to the development of depression and anxiety.

Where do prebiotics fit into this narrative?

Alongside a diverse diet, prebiotics significantly contribute to the diversity of the gut microbiome. Logically, due to their chemical properties, our bodies do not metabolize them; instead, probiotics and their ‘hungry brethren’ in the intestines eagerly receive them intact. By consuming prebiotics, we are literally and figuratively feeding the members of the gut microbiome that depend on them, thereby creating conditions for their growth and development.

Long-term intake of prebiotics will ensure diversity within the gut microbiome, even in suboptimal conditions such as a lack of diverse diet, travel, inadequate sleep, or antibiotic intake. However, it’s crucial to consider the intake of prebiotics carefully. Prolonged consumption of specific types of prebiotics can lead to the selection of bacteria that can best utilize them, potentially impacting diversity negatively. Hence, within the context of a healthy diet for the gut microbiome, there’s increasing mention of the paradigm of consuming 20 to 30 different types of plant-based foods (vegetables, fruits, legumes) weekly.

Each plant-based food carries its unique combination of prebiotic compounds, fibers, and polyphenols. Consuming these supports the growth of specific groups of bacteria. It’s through the diverse intake of prebiotics that substrates are provided for all members of the gut microbiome, ensuring their balanced growth.

If the number of 20 to 30 plant species per week seems overwhelming, it’s essential to note the phenomenon within the gut microbiome called ‘cross-feeding.’ When the gut microbiome composition is ideal, consuming a specific prebiotic will stimulate the growth of certain bacteria that, through their metabolites, will nourish other members of the gut microbiome. This phenomenon has been observed with traditional bifidogenic substances, prebiotics from the oligosaccharide group, which promote the growth of bacteria from the Bifidobacterium genus. These bacteria produce lactate, lactic acid, which serves as a substrate for the growth of anaerobic bacteria (e.g., from the Roseburia and Eubacterium genera) that produce butyrate. In this way, the intake of one type of prebiotic can provide conditions for the growth of a wide variety of bacteria, provided that there are bacteria present to facilitate ‘cross-feeding’ through their metabolites.

Through positive changes in the composition of the gut microbiome, in terms of balance and diversity, the intake of prebiotics will lead to improvements in the functionality of the gut microbiome. The gut microbiome will produce adequate amounts of metabolites necessary for the functioning of the gut-brain axis.

It’s no wonder, therefore, that prebiotics such as fructooligosaccharides (FOS) and galactooligosaccharides (GOS), proven bifidogenic agents in amounts of 5 grams per day, can alleviate the clinical presentation of depression and anxiety. Concerning the gut-brain axis, prebiotics can enhance resilience to stress and even promote sociability. Clinical confirmation has shown that a blend of prebiotics is more effective than the intake of a single type of prebiotic.

One such prebiotic preparation, which contains both fructo- and galactooligosaccharides, is OMNi-LOGiC® PLUS. Its composition stimulates the proliferation of the Akkermansia muciniphila bacterium, involved in gut barrier restoration, and Faecalibacterium prausnitzii, capable of producing butyrate, providing primary energy to the intestinal lining. Strengthening the connections between intestinal lining cells ensures the separation of beneficial nutrients from harmful ones.

The fascination with prebiotics stems from the fact that their intake promotes the growth of existing species. Unlike probiotics, where we introduce new species that, if they don’t colonize our gut microbiome, only have transient effects on it, the intake of prebiotics lays the foundation for a healthy gut microbiome. If it isn’t balanced, a cascade of changes occurs in the body — from the gut barrier to the immune system — subsequently leading to disturbances in the gut-brain axis, with negative consequences for our mental and emotional well-being.

Before suddenly and unexpectedly introducing large quantities of various prebiotics, it’s important to note that this will lead to short-term digestive issues. This is completely understandable; if the gut microbiome isn’t accustomed to certain amounts of prebiotics, uncontrolled fermentation and gas production occur, generating methane and hydrogen. This happens, for instance, when there’s an excess of beans or other vetch. However, if prebiotics are introduced gradually, ‘cross-feeding’ will develop, and bacteria will emerge that, through their metabolism, reduce gas production. Bloating from legumes doesn’t mean they are the problem; rather, it’s due to the infrequent exposure of the gut microbiome to them.

That’s why prebiotics form the cornerstone of a healthy gut microbiome, and while transient bloating may be socially uncomfortable, in the long run, it leads to improved sociability. Our microbial tenants need sustenance for life just as much as we do. Although they can benefit from ‘cross-feeding,’ unlike us, they also have their preferences and needs when it comes to food. But they don’t require much—just a few grams to fulfill their psychobiotic potential. Prebiotics truly are important!

Adapted from:

Centar Mikrobiom d.o.o.

Sky Office, Toranj B

R. F. Mihanovića 9, Zagreb, Croatia

Mob.: + 385 98 13 73 344

Tel.: + 385 1 78 99 694

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