People often experience “butterflies in their stomach” or a “gut-wrenching” feeling in the face of stressful situations, but what does this entail? Is it just our imagination, or can the gut be communicating with us?  

Figuratively speaking, our gut may indeed have a brain of its own! In addition to our central nervous system (CNS), where our brain is located, the gut is lined with an extensive network of nerves that is responsible for controlling our digestion, called the enteric nervous system (ENS). While the ENS is not capable of having tangible thoughts, it can communicate back and forth with the CNS.  

This intimate connection between the gut and brain is powerful enough that the mere thought of eating food can result in the release of digestive juices into the stomach, before we even put any food in our mouths. This crosstalk also provides an explanation for why individuals feel nauseous when they are nervous before a presentation, or why students experience diarrhea on the day of an exam. This “gut-brain axis” may also be the underlying cause for why individuals with chronic gut pathologies, such as Inflammatory Bowel Syndrome, are also at greater risk for developing depression and anxiety. These phenomena raise the interesting concept that mental health can directly impact our physical well-being, and vice versa. Another convincing piece of evidence that this gut-brain connection is real is that certain antidepressants, cognitive behavioural therapies, and even medical hypnosis are effective at treating bowel diseases, providing interesting insights from a therapeutic perspective. 

In addition to communicating with the brain, the gut serves as a hub that receives signals from the external environment. It is home to billions of microorganisms, termed the gut microbiota, who play an important role in promoting or deteriorating gut health. They act as orchestrators of the gut-brain connection through manipulating the physical gut environment. In other words, our brain is subconsciously communicating with our gut microbiota and in turn, they also relay messages to our brain. With the help of animal models, where we can manipulate the gut microbiota or level of psychosocial stress, we have been able to decipher what many of these messages entail at the molecular level. Below we will explore a few of these discoveries.  

Microbiota can produce neurotransmitters 

Neurotransmitters are the chemical signals that pass through the nervous system, allowing for communication between the CNS and environmental stimuli. Some of these chemicals, such as serotonin, are natural mood boosters, where increased levels in the body can stave off depression and create a euphoric feeling. 90% of the serotonin necessary for CNS and gut functions, such as those controlling sleep and behaviour, is produced in the gut. Contributing to this number are various species of gut-resident bacteria that not only produce serotonin, but also other neurotransmitters like acetylcholine. These bacteria also produce serotonin precursors like the amino acid, tryptophan.  

Microbiota can promote inflammation 

The microbes that colonize our digestive tract have the potential to both promote or deter gut health.  Inflammatory bowel diseases are often the product of an unhealthy shift in the gut microbiota composition. Such a shift could arise due to various environmental changes, including antibiotic usage, high fat diet, or infections. Our immune system is constantly surveying the gut, and these potentially harmful gut colonizers can trigger immune cells both in local and distally located regions of the body to release inflammatory proteins, called pro-inflammatory cytokines. Cytokines produced by gut macrophages, for example, can enter the blood and circulate to the CNS, where they can structurally damage or alter our nervous system, leading to subsequent cognitive impairment. Heightened inflammation in the CNS can, therefore, result in functional changes that impact mood and behaviour. Alternatively, chronic stress and associated stress hormones can lead to changes in the microbiota population, also promoting inflammation.  

Microbial metabolites can directly impact CNS function 

In the healthy gut, microbes can produce short chain fatty acids (SCFAs) by digesting dietary fibers. These SCFAs not only protect against intestinal and CNS inflammation, but they may also exert direct effects on the CNS through promoting nerve cell growth and function. A notable example of this scenario is the ability of the SCFA, butyrate, to trigger the release of neurotrophic factors in the brain hippocampus, which are proteins that promote the survival and growth of nerve cells. The resulting increase in nerve cell connectivity in this brain region, in the presence of butyrate, was observed to reduce rodent anxiety. 

These observations in animal models can pave the way for more focused studies to uncover the mechanisms linking our gut to mental health. The microbiota is diverse, ever-changing, and malleable, making it an enticing target to treat both neuropsychiatric and gastrointestinal disorders, seeing as how these microbial messengers are potentially relaying messages along the gut-brain axis. Psychobiotics, which use microbiota interventions to promote mental health, can be the next trend in mental wellness.  


Sources  

Barichello, T., Generoso, J. S., Simões, L. R., Faller, C. J., Ceretta, R. A., Petronilho, F., Lopes- 

Borges, J., Valvassori, S. S., & Quevedo, J. (2015). Sodium Butyrate Prevents Memory Impairment by Re-establishing BDNF and GDNF Expression in Experimental Pneumococcal Meningitis. Molecular Neurobiology, 52(1), 734–740. 

Bray, N. (2019). The microbiota–gut–brain axis. Nature Research. https://doi.org/10.1038/d42859-019-00021-3

Cryan, J. F., O’Riordan, K. J., Cowan, C. S., Sandhu, K. V., Bastiaanssen, T. F., Boehme, M., … & Dinan, T. G. (2019). The microbiota-gut-brain axis. Physiological reviews. Retrieved May 27, 2022, from https://journals.physiology.org/doi/full/10.1152/physrev.00018.2018  

Marrocco, F., Delli Carpini, M., Garofalo, S., Giampaoli, O., De Felice, E., Di Castro, M. A., Maggi, L., Scavizzi, F., Raspa, M., Marini, F., Tomassini, A., Nicolosi, R., Cason, C., Trettel, F., Miccheli, A., Iebba, V., D’Alessandro, G., & Limatola, C. (2022). Short-chain fatty acids promote the effect of environmental signals on the gut microbiome and metabolome in mice. Communications Biology, 5(1), 517. 

Rege, S., & Graham, J. (2017, June 27). The Simplified Guide to the Gut-Brain Axis – How the Gut Talks to the Brain. Psych Scene Hub. https://psychscenehub.com/psychinsights/the-simplified-guide-to-the-gut-brain-axis/ 

Silva, Y. P., Bernardi, A., & Frozza, R. L. (2020). The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication. Frontiers in Endocrinology, 0. https://doi.org/10.3389/fendo.2020.00025 

The gut-brain connection. (2021, April 19). Harvard Health. https://www.health.harvard.edu/diseases-and-conditions/the-gut-brain-connection

The Brain-Gut Connection. (2022). John Hopkins Medicine. https://www.hopkinsmedicine.org/health/wellness-and-prevention/the-brain-gut-connection

Yang, L. L., Millischer, V., Rodin, S., MacFabe, D. F., Villaescusa, J. C., & Lavebratt, C. (2020). Enteric short-chain fatty acids promote proliferation of human neural progenitor cells. Journal of Neurochemistry, 154(6), 635–646. 

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