You are what you eat—the other brain in the human body

When we think of the nervous system, we most often think of the central nervous system (CNS), which is made up of the brain and spinal cord. We also think of nerves, which are bundles of neurons extending from the CNS to all other parts of the human body. These nerves form the peripheral nervous system (PNS), and are responsible for relaying information from the brain to organs and limbs [1]. Motor neurons take signals from the brain and interact with muscles, controlling our conscious and unconscious physical motions. Sensory neurons work the other way, picking up signals from the skin and other organs and sending them back to the brain to process. 

The largest collection of neurons in one organ is in the gastrointestinal tract, which scientists call the enteric nervous system (ENS). We find evidence of the ENS in organisms throughout history, spanning from insects and crustaceans to mammals [2]. Some of these organisms, such as Hydra (tiny, jellyfish-like animals) don’t have a CNS! This suggests that sometime during the evolution of more complex organisms, there was a redistribution of neurons to separate conscious tasks, like thinking, from unconscious tasks, like maintaining a heartbeat.

In humans, the ENS has many functions, from helping with digestion to influencing your mood [3]. Motor neurons of the ENS control the movement of food through the intestines in a process called peristalsis; this process allows for maximal nutrient absorption. Sensory neurons in the ENS communicate with the CNS to make us feel hungry, full or even nauseous. Enteric neurons can release chemicals called cytokines that influence the development of specific immune cell populations to protect the gut from infection and autoimmunity (the immune system attacking the healthy body) [4]. Some neurons also interact with bacteria naturally present within the intestine, and this communication has been directly linked to changes in mood and behavior.

The ENS also interacts with the cells lining the intestine to keep the gut healthy. Our small intestine is lined with a single layer of cells, and this entire lining is regenerated roughly every week. Enteric neurons are essential for this regeneration, and the intestinal structure is disturbed when parts of the ENS are damaged [2]. Signals from the ENS directly help the cells of the lining connect to each other to form an intact barrier, thereby reducing the risk of infection by gut bacteria.

There is still a lot that we don’t know about the ENS, especially related to the interactions between enteric neurons and other cell types in the gut, as well as with cells of the CNS. Many ongoing research efforts are interested in understanding how the ENS and CNS interact in gastrointestinal and neurological disorders. After all, the ENS is the “second brain” of the human body!

References

[1] SEER Training Modules, Nervous System. U. S. National Institutes of Health, National Cancer Institute. https://training.seer.cancer.gov/anatomy/nervous/

[2] Sharkey, K. A. and Mawe, G. M. (2023). The Enteric Nervous System. Physiol Rev. https://doi.org/10.1152/physrev.00018.2022

[3] Rao, M. and Gershon, M. D. (2016). The bowel and beyond: the enteric nervous system in neurological disorders. Nat Rev Gastroenterol Hepatol 13, 517–528. https://doi.org/10.1038/nrgastro.2016.107

[4] Wang, H., Foong, J.P.P., Harris, N.L. et al. (2022). Enteric neuroimmune interactions coordinate intestinal responses in health and disease. Mucosal Immunol 15, 27–39 https://doi.org/10.1038/s41385-021-00443-1

Image created by Ananya Parthasarathy in BioRender

Edited by Emma Hays