Gut Feelings: The Connection With The Brain

Picture this: You are encountering some dilemma. You call your friend, and they advise you to go with your “gut feelings”. These are perceived to be some sort of miraculous instincts that we are supposed to rely upon when experiencing uncertainty. They magically know your deep desires and wishes; your likes and dislikes. They consciously affect your decisions. It is plausible to speculate that the gut and the brain might be somehow connected. Well, they are! But how?

Microbial mind control

Your body is a collection of microbes (including bacteria, fungi, viruses, and archaea). In fact, there are ten times more microbial cells in your body than human cells! The majority of them live in your gut and are termed the ‘gut microbiome’. We live in a symbiotic relationship with our microbiome – sort of like sharing a room with someone who does not pay rent but helps out with chores. We provide them a home, and they perform a plethora of functions for us. They help in digestion, boost the immune system, and can even modulate our emotions. But how? The gut and the brain “communicate” with each other. It appears that bacteria are able to produce and respond to different neurochemical signals, which travel to and from the brain. Gut microbiota can affect the brain function by activation of the vagus nerve – which acts as a “connecting highway“ between the two (the mechanism of activation is not entirely understood). They also produce signaling molecules, like short-chain fatty acids (SCFAs) – a product of metabolism of carbohydrates that can’t be digested by our body. These, in turn, can activate some receptors (GPCRs) in the brain. Consider SCFAs as keys to the locks in the brain that can impact behavior.

The second brain

As we all know, neurons are brain cells that transmit signals in the nervous system. The nervous system is made up of different parts and the neurons lining the gut, or gastrointestinal tract from the mouth to the anus, comprise the so called Enteric Nervous System (ENS). In total, the ENS contains over 100 million neurons (more than in the spinal cord!) and because this vast web of connections is so extensive, scientists have given it the nickname of “second brain”. The nickname is well earned not only due to the number of neurons comprising the ENS, but also due to its intimate interactions with our microbiota. Our microbiota are a major source of molecules called neurotransmitters which are responsible for transmitting a signal from one neuron to the next. Due to their role in neurotransmitter production, the microbiota are able to illicit strong influence over the neural signaling happening in our ENS and hence form a complex system worthy of the name the “second brain”.

The microbiota is also major source of several of these chemical messengers. For example, abundant evidence supports the role of gut bacteria in the production of serotonin (also known as the happy neurotransmitter). This neurotransmitter is produced primarily through the break-down of a naturally occurring amino acid called tryptophan by enteroendocrine cells. This process is influenced by SCFAs that increase the amount of the enzyme – tryptophan hydroxylase – responsible for tryptophan metabolism and conversely, if levels of SCFAs drop then serotonin production by the gut microbiome also lowers. One of the main sources of SCFAs comes from what we eat and therefore our diet plays a critical role in balances of molecules and metabolites in our gut affecting many processes such as serotonin production. Because of this delicate balance any perturbation in the gut microbiome might also impact the brain and visa versa.

That sinking feeling in the pit of your tummy when you are writing a difficult test is a vivid example of the brain-gut connection at work. You’re stressed and your gut knows it! Think about the time when you had to give an important presentation and you found yourself looking for a bathroom. Or the night when you were upset and found yourself craving some comfort food.

“For decades, researchers and doctors thought that anxiety and depression contributed to digestive problems. But several studies reveal that it may also be the other way around,” explains Jay Pasricha, M.D., director of the John Hopkins Center for Neurogastroenterology. These bacteria can influence our perception of the world and alter our behavior far beyond the extent of what we have yet understood.

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Edited by Holly Hake and Arielle Hogan.

Illustrated by Gil Torten.

Translated by Elmer Sandoval.

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References

Emeran A. Mayer, (2011). Gut feelings: the emerging biology of gut-brain communication. Nature Reviews. Neuroscience, 12(8), 453-466. https://doi.org/10.1038/nrn3071

Lihua Ye, Rodger A. Liddle, (2017). Gastrointestinal Hormones and the Gut Connectome. Current Opinion in Endocrinology, 24(1), 9-14. https://journals.lww.com/co-endocrinology/toc/9000/00000

Pochu Ho, David A. Ross, (2016). More Than A Gut Feeling: The Implications of the Gut Microbiota in the Psychiatry. Elsevier, 86(5), 411-423. https://doi.org/10.1016/j.biopsych.2016.12.018

Mikala Egeblad, (2020). Gut Feelings Block the Flow: Microbiota Links Stress to Vascular Disease. Immunity, 53(2), 417-428.
https://doi.org/10.1016/j.immuni.2020.07.013