Our gut feeling rarely lets us down, although we know very little about how it happens. As science discovers more about the connection between the gut and brain, the role of the little-known and rare enterochromaffin (EC) cells becomes central to our understanding of how the brain and gut communicate. We have all felt butterflies or that wrenching feeling in our stomach when we are anxious, and we also know that long term anxiety and depression often leads to various disorders of the gastrointestinal (GI) tract. We have known for some time about that our mental state can affect the gut, and what we are discovering now with the help of modern research is how gut health affects the brain and general well-being. These days, it seems that what has been missing from this cyclic relationship is our understanding of EC cell functions.

Basic features of the gut-brain axis

To fully appreciate the role of EC cells, we have to delve into some basic underlying concepts and facts. Our gut has more neurons than our spine or peripheral nervous system—that is why it is also known as the second brain. These neurons have various functions, like controlling gut motility, protecting against irritants (through increased motility or vomiting), and many other still to be understood functionalities. These gut neurons mostly work independently from the brain, but when required, they send information and get feedback from the brain, thus functioning as a closed loop often called the gut-brain axis.

EC cells play a vital part in the gut-brain axis. These cells have receptors that are always listening to various activities in the gut and sending feedback to the brain and other neurons of the gut through chemical messengers or hormones. Although EC cells have functional similarities to glands, they are spread all over the digestive tract, and they form about one percent of the gut epithelium. Although one percent may sound small, EC cells secrete more than 30 kinds of hormones and neurotransmitters (this number will likely increase as more are identified). In fact, they secrete more than 90% of the body’s serotonin, a neurotransmitter well-known for its role in various mental states, including mental disorders like depression and anxiety.

Now, it is well understood that the communication between the brain and gut is double-sided, forming a loop. Thus, mental distress causes gut disorders, and gut disorders may influence mental states. Moreover, EC cells have a critical role in this entire axis.

Brain and GI disorders

Stress is known not only to cause GI disorders, but it also makes the symptoms worse. Stress and psychological factors change the movement of the GI tract, worsen inflammatory processes, and even increase susceptibility to various infections. In all of these processes, EC cells play a crucial role. The release of serotonin from EC cells is the key mechanism for controlling the motility of the gut. They can be stimulated due to local irritation, as well as through nerve supply, especially the vagus nerve. Therefore psychological therapy has a special place in treating functional GI diseases, along with pharmaceutical therapy. EC cells are highly sensitive to the effect various chemical compounds like detergents and spices. They have been demonstrated to even have olfactory receptors—yes, the same receptors that are present in our nose.

Gut and brain disorders

Although the effect of mental stress on GI function has been known for ages, in recent times there has been increased interest in better understanding the influence of gut health on the brain. This became particularly important after research demonstrated that EC cells not only have an indirect influence on nerves through serotonin, they also seem to have direct links with neurons. Thus, EC cells appear to be directly connected to the brain. This means that changes in the gut are transmitted to the brain in milliseconds, and not in seconds or minutes as previously thought.

This fact gains further importance, considering that the vagus nerve (the main nerve connecting the brain and GI) has more afferent fibers (those sending a signal to the brain) than efferent fibers (those sending a signal from the brain to organs). These afferent fibers cause feelings like nausea when you eat the wrong kind of food. The role of these vagal signals from the GI to the brain and their relationship with other aspects of health are being investigated, like arousal, fatigue, and poor regulation of body temperature, and may become the target of future therapies.

Treatment strategies targeting the gut-brain axis

Many drugs for mental distress like depression have been used effectively to treat gut disorders. Inflammatory bowel syndrome (IBS) is one of the most prevalent of such disorders. Some researchers even call it a “mental disorder of the gut”. Selective serotonin uptake inhibitors (SSRIs) have shown increasingly important roles in the management of this disorder. SSRIs help to control overactive EC cells. The role of SSRIs is not limited to the treatment of IBS. Their role is being studied in various functional diseases of the GI, in controlling nausea, diarrhoea, constipation, vomiting, and many other disorders.

To date, the same SSRIs that are used to treat mental health issues are being used to deal with GI problems. However, many clinical researchers are studying non-absorbable serotonergic agents for GI disturbances. Further studies are being done to target tryptophan hydroxylase, a precursor for the synthesis of serotonin.

The role of EC cells in gut functioning is being investigated in depth to better understand and treat disorders of the brain like dementia, Alzheimer’s disease, Parkinsonism, and autism. As we learn more about EC cells, we might be able to treat many medical illnesses more effectively.

References

Andrews, P.L.R., Sanger, G.J., 2002. Abdominal vagal afferent neurones: an important target for the treatment of gastrointestinal dysfunction. Curr. Opin. Pharmacol. 2, 650–656. doi: 10.1016/S1471-4892(02)00227-8.

Bellono, N.W., Bayrer, J.R., Leitch, D.B., Castro, J., Zhang, C., O’Donnell, T.A., Brierley, S.M., Ingraham, H.A., Julius, D., 2017. Enterochromaffin Cells Are Gut Chemosensors that Couple to Sensory Neural Pathways. Cell 170, 185–198.e16. doi: 10.1016/j.cell.2017.05.034.

Braun, T., Voland, P., Kunz, L., Prinz, C., Gratzl, M., 2007. Enterochromaffin Cells of the Human Gut: Sensors for Spices and Odorants. Gastroenterology 132, 1890–1901. doi: 10.1053/j.gastro.2007.02.036.

Dunlop, S.P., Jenkins, D., Neal, K.R., Spiller, R.C., 2003. Relative importance of enterochromaffin cell hyperplasia, anxiety, and depression in postinfectious IBS. Gastroenterology 125, 1651–1659. doi: 10.1053/j.gastro.2003.09.028.

Mawe, G.M., Hoffman, J.M., 2013. Serotonin signalling in the gut—functions, dysfunctions and therapeutic targets. Nat. Rev. Gastroenterol. Hepatol. 10, 473–486. doi: 10.1038/nrgastro.2013.105.

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