Scattered throughout the lining of the digestive tract are specialized endocrine cells known as enterochromaffin (EC) cells. Although they are a small fraction of all epithelial cells, they form the largest population of hormone-producing cells in the digestive system. These cells act as communicators, translating information from the gut lumen to the body’s nervous, immune, and digestive systems. Their location allows them to monitor intestinal contents and respond by releasing signaling molecules.
The Serotonin Powerhouses of the Gut
Enterochromaffin cells are the principal source of the body’s serotonin, a signaling molecule. While many associate serotonin with its functions in the brain, approximately 90-95% of the body’s total supply is produced and stored within these gut cells. This peripheral serotonin is chemically identical to the one in the brain but is synthesized by a different enzyme. EC cells use Tryptophan hydroxylase 1 (TPH1) to convert the amino acid tryptophan into serotonin, whereas neurons use a distinct enzyme, TPH2.
Once synthesized, this serotonin (also called 5-hydroxytryptamine or 5-HT) is packaged into vesicles inside the EC cells for rapid release when stimulated. While serotonin is their main product, EC cells also secrete other substances like ATP and guanylin that participate in gut signaling. The quantity of serotonin produced highlights their role in regulating local gut functions, separate from the central nervous system.
The production of serotonin by EC cells is not constant and is influenced by external factors. Metabolites from the gut microbiota, like short-chain fatty acids, can increase the expression of the TPH1 enzyme, boosting serotonin synthesis. This process connects diet and microbial health to the body’s serotonin levels.
Regulators of Digestion
The serotonin released from EC cells acts as a local hormone that modulates digestion. A primary role is controlling gut motility, the muscular contractions that propel food through the intestines. When released, serotonin binds to nerve cells in the enteric nervous system—the gut’s intrinsic “brain.” This interaction triggers the peristaltic reflex, ensuring the efficient movement of intestinal contents.
Serotonin also governs fluid secretion into the gut. It stimulates the intestinal lining to release chloride ions, causing water to follow, which helps lubricate and break down food. This process is important for maintaining the right consistency of stool.
Beyond movement and secretion, serotonin is a factor in visceral sensation, which is how we perceive feelings like fullness, bloating, and pain from our gut. High concentrations of serotonin can activate sensory nerve fibers that send signals to the brain, leading to sensations of discomfort or nausea. The molecule also influences blood flow within the gut wall, matching circulatory supply to the metabolic demands of digestion.
Sensing the Gut Environment
Enterochromaffin cells function as sensory cells, monitoring the environment within the gut lumen. They have receptors that detect chemical signals from digested food, including sugars, fats, and amino acids. By sensing these nutrients, EC cells help coordinate the digestive response, releasing serotonin to manage motility and secretion according to the meal’s composition.
These cells are also mechanosensors that detect physical forces. The stretching of the gut wall as food passes, known as mechanical distension, triggers EC cells to release their contents. This is made possible by specialized ion channels, like Piezo2, which convert physical force into an electrical signal within the cell, leading to serotonin release.
EC cells play a defensive role by detecting irritants, toxins, and byproducts from pathogenic bacteria. When they sense a harmful substance, they initiate a protective response by releasing serotonin to increase gut motility and fluid secretion. This action helps flush the offending substance from the system, contributing to symptoms like diarrhea. Their sensitivity also extends to changes in pH and signals from the resident gut microbiota.
When EC Cells Malfunction
Dysfunction of enterochromaffin cells is linked to several gastrointestinal disorders. In irritable bowel syndrome (IBS-D), patients may have a higher number of EC cells or their cells may be overactive. This leads to excess serotonin in the gut, causing rapid transit, increased fluid secretion, and heightened pain sensitivity.
In inflammatory bowel diseases (IBD) like Crohn’s disease and ulcerative colitis, the role of EC cells is also notable. Chronic inflammation from IBD can alter the number and function of these cells. The serotonin they release can contribute to the inflammatory cascade, influencing immune cells and exacerbating fluid loss in the inflamed gut tissue.
A direct consequence of EC cell malfunction is the development of neuroendocrine tumors, specifically carcinoid tumors. These slow-growing cancers arise from EC cells and produce large quantities of serotonin. When this overproduction becomes systemic, it can lead to carcinoid syndrome, a condition marked by severe diarrhea, skin flushing, wheezing, and sometimes damage to heart valves.