Exploring the Gut-Brain Connection: Part 1

What is the Gut-Brain Connection?

Everyone knows we have a brain in our skull, which is part of the central nervous system. What is increasingly well known is that we have a second brain in our gut! Fascinatingly, this “belly brain” houses the same types of neurons and neurotransmitters found in the brain in our skull. Neurotransmitters are chemical messengers that can increase or decrease activity of various body systems. Along with nerves, these neurons and neurotransmitters are found along the entire digestive tract (“gut”) and monitor and regulate the digestive system [1], hence the name “belly brain”. This belly brain is technically known as the enteric nervous system and contains two thin layers of more than 100 million nerve cells lining the gut [1]! The belly brain plays a role in many facets of life, including digestion, health, mood regulation, sleep cycles and stress response, along with immune system function and inflammation. If you don’t think the food you consume is important, think again…

Two-Way Conversation Between Gut and Brain

 Research has proven that the brain in our skull and our belly brain are actually linked and information travels both from brain to gut AND gut to brain! Have you ever noticed that when you get stressed your stomach starts to hurt or you feel sad and want a cookie? That’s your brain signaling to your gut. Have you ever noticed that eating certain foods, like fresh fruit or chocolate, make you feel really happy? Or how that morning cup of coffee perks you up? That’s information traveling the other way, from your gut to your brain. The gut and brain are in constant communication along the gut-brain axis and information travel is bidirectional, meaning both gut and brain are sending messages to each other all the time.

Introducing the Microbiome Chemical Factory

 On the gut-brain axis, there are various pathways in which the information travels, including via neurotransmitters and hormones, immune system cells, the vagus nerve and the gut microbiome. These are not independent pathways, but highly connected networks of communication. First off, the gut microbiome is the community of microorganisms, including bacteria, bacteriophage, fungi, protozoa and viruses, and their genetic material that live in the gut [2]. The gut microbiome has over 1000 species of bacteria and 7000 subspecies [3]! These different bacteria serve different functions and also produce different neurotransmitters. Some bacteria are helpful and protective, while some are harmful; it’s the ratio of helpful to harmful that regulates if, when and how much of certain neurotransmitters are produced. Certain bacterial families actually synthesize neurotransmitters. For example, Lactobacillus and Bifidobacterium create GABA, a calming neurotransmitter that fosters relaxation and good sleep.  Candida, Streptococcus, Escherichia and Enterococcus create serotonin, the “feel good” neurotransmitter crucial for positive feelings, calming, sleep and control over addictive behavior. Norepinephrine is synthesized by Escherichia coli, Bacillus and Saccharomyces and acts a neurotransmitter for attention, emotion and learning and also as a hormone for heart rate and blood pressure regulation. The “reward” neurotransmitter dopamine is created by Bacillus and Serratia bacteria strains and plays a role in cognition, emotional regulation, motivation and feelings of pleasure [3]. Neurotransmitters also function to regulate gut movement, blood flow and nutrient absorption [4].

Did you know that 70% of the body’s serotonin is created in the gut? The microbiome is responsible for production and regulation of serotonin levels, but it doesn’t just stay in the gut. Certain strains of bacteria can disable the serotonin receptors in the brain, limiting the amount of serotonin available in the frontal lobe. This can affect movement, behavior, emotions and perception of pain [5].

The Vagus Nerve Superhighway

 Now you’re probably wondering how do all these bacteria and neurotransmitters in the gut affect the brain? Enter the vagus nerve that connects the gut and the brain. The vagus nerve, the tenth cranial nerve, is actually a set of nerves and they run from the brainstem down into the abdomen and colon, with many branches along the way. The vagal pathways serve as a direct link to relay information from the gut to the brain and from the brain to the gut. These pathways even have inflammatory markers on them to identify and flag invaders for removal [6]. The vagus can control the movement of the gut, impacting digestion, heart rate, functioning of other internal organs, immune responses and even your brain state [7]. Interestingly enough, research shows that the gut loses its communication with the brain when the vagus nerve is severed, shown by the lack of behavioral changes in mice with altered gut microbes [8].

Networked with the vagus nerve is the hypothalamic-pituitary-adrenal (HPA) axis, which connects the hypothalamus and pituitary glands in the brain to the adrenal glands, above the kidneys. Let’s call this the stress axis, as it is the highway that the brain sends information down to regulate the stress response. This stress axis uses hormones to control digestion [9] and is activated by both environmental stress (like your job) and internal stress (like inflammation). Research shows only 2 hours of social stress is enough to create changes in the microbiome. When stress is experienced, the hypothalamus releases inflammatory hormones, which, in turn, stimulate the release of more inflammatory hormones from the pituitary glands, which then yield cortisol release from the adrenal glands [8]. This sends the body into widespread activation and inflammation, turning off “rest and digest” and preventing calming hormones from being released. Fortunately, a healthy microbiome has the ability to regulate this response, so having enough good bacteria in your gut can prevent this cascade of stress in the body and leave you more resilient [8]. The vagus nerve can also signal the stress axis to release hormones that suppress inflammation and promote healthy digestion and nutrient absorption [10].

Defending Against Invaders

 Another form of communication between the gut and brain is the immune system. Also using the vagus nerve as an information highway, the immune cells in the gut can signal to the immune cells of the brain, which are called microglia. Microglia locate and attack injuries or invaders in the brain. They can release inflammatory compounds, which can lead to mood changes, pain or neurodegenerative diseases, but they also release growth factors that keep the brain healthy and resilient [11]. If the microbiome has gotten out of balance, it likely has allowed the intestinal barrier to be compromised. Loosened tight junctions in this barrier can allow bacteria, bacterial metabolites and other inflammatory compounds into the body [8]. These bacteria stimulate immune cells to release inflammatory proteins that travel in the bloodstream up to the brain, where they can affect the development and function of microglia. Some of this material can cross the blood-brain barrier and negatively impact brain function [3]. Other parts of this material are picked up by the inflammatory markers on the vagus nerve, which then tells the brain to suppress inflammation by releasing calming hormones [6].

All of these components- the immune system, stress axis, vagus nerve and microbiome, work elegantly together to facilitate bidirectional communication between the brain and the gut. This has been just a snapshot of the current research, there are still many developing theories being tested and new research comes out frequently. Having a healthy microbiome fosters a healthy brain and supporting brain health improves gut health. Stay tuned for how to heal and rebalance the gut-brain axis in an upcoming blog post or newsletter!

Article by Heather Hill, Peakneurofitness LLC, Client Care Manager

Original artwork by Kaela Peters

References

[1] The Brain-Gut Connection. https://www.hopkinsmedicine.org/health/healthy_aging/healthy_body/the-brain-gut-connection

[2] The Human Microbiome Project: Extending the definition of what constitutes a human. (n.d.). Retrieved from https://www.genome.gov/27549400/the-human-microbiome-project-extending-the-definition-of-what-constitutes-a-human/

[3] Evrensel, A., & Ceylan, M. E. (2015). The Gut-Brain Axis: The Missing Link in Depression. Clinical Psychopharmacology and Neuroscience, 13(3), 239-244. doi:10.9758/cpn.2015.13.3.239

[4] Mittal, R., Debs, L. H., Patel, A. P., Nguyen, D., Patel, K., Oconnor, G., . . . Liu, X. Z. (2017). Neurotransmitters: The Critical Modulators Regulating Gut-Brain Axis. Journal of Cellular Physiology,232(9), 2359-2372. doi:10.1002/jcp.25518

[5] Malinova, T. S., Dijkstra, C. D., & Vries, H. E. (2017). Serotonin: A mediator of the gut–brain axis in multiple sclerosis. Multiple Sclerosis Journal,1-7. doi:10.1177/1352458517739975

[6] Brogan, K. (2018, April 26). From Gut to Brain: The Inflammation-Depression Connection. http://kellybroganmd.com/from-gut-to-brain-the-inflammation-connection/

[7] Zhu, X., Han, Y., Du, J., Liu, R., Jin, K., & Yi, W. (2017). Microbiota-gut-brain axis and the central nervous system. Oncotarget,8(32), 53829-53838. doi:10.18632/oncotarget.17754

[8] Carabotti, M., Scirocco, A., Maselli, M. A., & Severi, C. (2015). The gut-brain axis: Interactions between enteric microbiota, central and enteric nervous systems. Annals of Gastroenterology,28(2), 203-209.

[9] Sonnenburg, J., & Sonnenburg, E. (2015, May 01). Gut Feelings–the “Second Brain” in Our Gastrointestinal Systems [Excerpt]. https://www.scientificamerican.com/article/gut-feelings-the-second-brain-in-our-gastrointestinal-systems-excerpt/

[10] Bonaz, B., Sinniger, V., & Pellissier, S. (2017). The Vagus Nerve in the Neuro-Immune Axis: Implications in the Pathology of the Gastrointestinal Tract. Frontiers in Immunology,8. doi:10.3389/fimmu.2017.01452

[11] Fields, R. D. (2011). The other brain: The scientific and medical breakthroughs that will heal our brains and revolutionize our health. New York: Simon & Schuster.

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