Chemical Messengers Link Gut-Brain connection

Since the era of the microbiota reloaded in the late past century, we have come to realize how our gut bugs may shape our life. It now widely accepted that our gut microbiota, this life-long companion, is key to our health and well-being. 

Our gut not only contains our microbiota, but it also hosts up to 600 million neurons. These nervous system starts developing after conception, even before the first neuron in our foetal brain. Popular wisdom has always recognized that the gut is our “second brain”, but it seems that it may well be our first brain. 

Our brain is continually receiving and processing information from the exterior as well as the interior. It is now believed that up to 60-80% of the internal information received by the brain comes from the gut. This strong bidirectional connection between the gut and the brain is called the “Gut-Brain Axis” or (GBA). 

But why is this Gut-brain Axis so important? 

One of the key players in this bi-directional link is, of course, our gut microbiota.

Your microbiota uses this vital link to make itself be noticed. It sends chemical signals up to your brain through this Axis. It is now believed that those sugar cravings at night might not be you brain spoiling your diet, but a temper tantrum from specific bacteria in your gut that are not getting the food they were used to receive. Once you eat the candy, the microbiota releases sugars and certain fatty acids that give you this temporary “high”. The jury is still out if microbiota is responsible for the “follow up regret” or is just your mind being hard on itself.

Your microbiota may affect your mood, as well. It seems that your microbiota would be running the show and affecting your behavior. This potential influence of your microbiota may have in your brain is the most provocative.

But this gut-brain connection not only stops there. Growing evidence shows that altered gut-brain communication seems to be correlated with some of the most predominant psychological disorders that plague western societies.

The list of conditions under research is growing, and an altered microbiota is often cited as a critical factor in severe conditions. These conditions range from depression linked to Irritable Bowel Syndrome (IBS), migraines, neurodegenerative diseases such as Alzheimer’s and Parkinson’s, to neuropsychiatry disorders as depression, anxiety, schizophrenia and even autism. Most of these disorders are characterized by distorted gut-brain communication that is influenced by external stimuli [1, 2].

What stresses your Gut-brain axis?

Everyday stresses can disrupt the microbiota in your gut, and thus, can impact the Gut-Brain-Axis [3, 4]. These stressors can include:

  1. Poor diets (high in ultra-processed food and low in vegetables and fruits)
  2. Poor lifestyle choices (alcohol abuse, smoking), 
  3. Recurrent courses of antibiotics, 
  4. Chronic stress
  5. Recurrent seasonal infections (that may be linked to a chronically depressed immunity)

How the gut communicates with the brain? 

Our gut microbiota feeds from the food we eat and produces by-product chemicals, just like a car running on fuel that sheds emissions.

However, beneficial bacteria produce by-products that are utilized by the gut and even can travel to distant organs like the brain. They act as small essential messengers relaying chemical information throughout your body. Some of these chemicals are now termed by scientists as "postbiotics". 

Some of such postbiotics are Short-Chain Fatty acids (SCFA), gamma-aminobutyric acid (GABA) or serotonin (the happy hormone). For example, a study showed that meals high in legumes that rise the production of acetate in the hindgut could have a distant effect and curb appetite in the brain [5]. 

Not all these messengers are derived from microbiota but may be activated or controlled by the microbiome. For example, Vitamin D has also been showing to influence the immune system due to its strong connection with the microbiota, suggesting it could be employed in combination with pre and probiotics to improve the immune response [6, 7].

What are psychobiotics?

Originally, back in 2013, psychobiotics were defined as “a live organism that, when ingested in adequate amounts, produced a health benefit in patients suffering from psychiatric illness. As a probiotic, these bacteria are capable of producing and delivering neuroactive substances such as gamma-aminobutyric acid and serotonin, which act in the gut-brain-axis”[8].

After 2017, the term psychobiotic was broadened to include prebiotics or the fibre that acts as food for the psychobiotic. In fact, is the combination of the prebiotic, the probiotic and the resulting postbiotics what would comprise as a more realistic definition of a psychobiotic. These metabolites include butyrate, serotonin, gamma-aminobutyric acid to name a few.

Although the idea of using probiotics to improve psychological well-being through the brain-gut axis first appeared as far as 1880 and were popularized with 1907 Metchnikoff's works on yoghurt and longevity [11], it was not until the last decade that this idea was tested in preclinical studies with varying degree of success. The outcome of these trials was highly dependent of each product tested and the complexity of the condition under observation.   

Psychobiotics are exciting news; Not all pre, pro or postbiotics may be classified as psychobiotics. For example, TMA derived from dietary choline is a compound believed to be a marker of cardiovascular risk. This would be an example of a postbiotic that is not linked to better outcomes, and couldn't be classified as a psychobiotic as it seems to have negative effects in our well-being.

Conclusions

We are still a long way from figuring out what exactly drives our mental well being and how we can intervene effectively. So far, we know that a happy, stable gut may contribute to bring peace to our brain [9, 10]. We are still very far from deciphering the complex and intricate relationship between the gut and the brain. However, psychobiotics may be well prove to be a first baby step towards this ambitious goal. 

[1] The Gut–Brain Axis and the Microbiome: Mechanisms and Clinical Implications. Vadim Osadchiy, Clair R. Martin and Emeran A. Mayer. Clinical Gastroenterology and Hepatology, 2019.

[2] The role of the brain–gut–microbiota axis in psychology: The importance of considering gut microbiota in the development, perpetuation, and treatment of psychological disorders. Michael Ganci, Emra Suleyman, Henry Butt and Michelle Ball. Brain and Behavior, 2019

[3] Gut microbiota–brain axis in depression: The role of neuroinflammation. Anelise S.Carlessi, Laura A. Borba, Alexandra I. Zugno, João Quevedo and Gislaine Z. Réus. European Journal of Neuroscience, 2019

[4] Stress and the gut microbiota-brain axis. Guadalupe Molina-Torres, Miguel Rodriguez-Arrastia, Pablo Roman, Nuria Sanchez-Labraca and Diana Cardona. Behavioural Pharmacology, 2019.

[5] R. C. Mollard, C. L. Wong, B. L. Luhovyy, G. H. Anderson. First and second meal effects of pulses on blood glucose, appetite, and food intake at a later meal. Appl Physiol Nutr Metab 2011 36(5):634 - 642

[6] From Probiotics to Psychobiotics: Live Beneficial Bacteria Which Act on the Brain-Gut Axis. Luis G. Bermúdez-Humarán, Eva Salinas, Genaro G. Ortiz, Luis J. Ramirez-Jirano, J. Alejandro Morales, and Oscar K. Bitzer-Quintero. Nutrients, 2019.

[7] Vitamin D and microbiota: Two sides of the same coin in the T immunomodulatory aspects. Lucia Malaguarnera. International Immunopharmacology, 2020.

[8] The psychobiotic revolution – Mood, Food, and the New Science of the Gut-Brain Connection – Scott C. Anderson, John F. Cryan, Ted Dinan – 2017. National Geographic Press – ISBN 9781426218460.

[9] Exercise influence on the microbiome–gut–brain axis. Alyssa Dalton, Christine Mermier, and Micah Zuhl. Gut Microbes, 2019.

[10] Diabesity and mood disorders: Multiple links through the microbiota-gut-brain axis. Aitak Farzi, Ahmed M. Hassan, Geraldine Zenz and Peter Holzer. Molecular Aspects of Medicine, 2019.

[11] The Prolongation of Life: Optimistic Studies (1907)

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