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Enteroendocrine cells release hormones and neurotransmitters to regulate nutrient absorption, digestion, motility, feeding behaviors, and sensory perception (1, 2, 3, 4).
Approximately 1% of the intestinal epithelium consists of enteroendocrine cells (EECs) (5).
Based on cytoarchitecture and location, EECs are divided into open and closed types. Open-type cells have a bottle-neck shape and microvilli that contact the intestinal lumen, allowing them to respond directly to luminal contents. Closed-type EECs remain associated with the basal membrane and lack luminal microvilli; they sense luminal signals through neural or humoral networks (5).
Enteroendocrine cells produce distinct hormones and signaling molecules according to their location in the gut.
| EEC subtype | Main location | Secreted products |
|---|---|---|
| A cells | Stomach, corpus | Ghrelin |
| D cells | Stomach, pylorus; proximal small intestine | Somatostatin |
| Enterochromaffin cells | Pyloric stomach; small and large intestine | Melatonin, serotonin, Substance P, plus minor GABA, CRH, guanylin, and secretin |
| G cells | Antral stomach; duodenum | Gastrin |
| I cells | Small intestine | CCK, serotonin |
| L cells | Distal small intestine and colon | GLP-1, GLP-2, PYY, serotonin |
| K cells | Small intestine | GIP, serotonin |
(6, 7, 8)
EECs sense bacterial tryptophan metabolites and activate enteric and vagal neuronal pathways. They also detect nutrients and microbial metabolites, coordinating antibacterial, mechanical, and metabolic branches of the intestinal innate immune response. Following luminal stimulation, EECs secrete hormones or neuronal messengers through calcium-dependent mechanisms (9, 10).
Short-chain fatty acids and branched-chain fatty acids, generated through microbial carbohydrate and amino-acid catabolism, can activate EECs through G protein-coupled receptors (10, 11, 12).
EECs are not distributed in a uniform ratio throughout the gastrointestinal tract. They exhibit plasticity and can revert to an intestinal stem-cell state after tissue damage or treatments such as chemotherapy and irradiation (1, 13, 14).
New technical approaches demonstrated that EECs arise from the endoderm, rather than the neuroectoderm, despite sharing functional features with neurons (1, 15).
EECs arise from pluripotent stem cells at the base of intestinal crypts and migrate along the crypt–villus axis. Differentiation occurs over approximately 2–6 days through three basic helix–loop–helix transcription factors. The same stem cells generate enterocytes, Paneth cells, and goblet cells in the intestinal villi and crypts (15, 16).
Hormones released by EECs act locally on neighboring cells, including immune cells, on nerve endings, or at distant sites such as pancreatic islets and the central nervous system. Their effects include changes in food intake, appetite, satiety, gastric emptying, intestinal transit, digestive enzyme release, nutrient transport, intestinal barrier function, insulin secretion, immune responses, and tissue growth (9).
EECs sense metabolites from commensal microbiota and coordinate antibacterial, mechanical, and metabolic branches of the intestinal innate immune response (17).
In 1960, EECs were found to express markers of neuronal differentiation. Because of these features, they were initially believed to originate from the neural crest and were termed neuroendocrine cells (18).
Human intestinal EECs constitutively express TLR-2 and TLR-4 transmembrane receptors, which recognize microbial-associated and pathogen-associated molecular patterns (19, 20, 21, 22).
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see also:
Enteroendocrine Cell & G-Protein Coupled Receptor 41 (GPR41)