Abstract
Serotonin, also known as 5-hydroxytryptamine (5-HT), is a metabolite of tryptophan and is reported to modulate the development and neurogenesis of the enteric nervous system, gut motility, secretion, inflammation, sensation, and epithelial development. Approximately 95% of 5-HT in the body is synthesized and secreted by enterochromaffin (EC) cells, the most common type of neuroendocrine cells in the gastrointestinal (GI) tract, through sensing signals from the intestinal lumen and the circulatory system. Gut microbiota, nutrients, and hormones are the main factors that play a vital role in regulating 5-HT secretion by EC cells. Apart from being an important neurotransmitter and a paracrine signaling molecule in the gut, gut-derived 5-HT was also shown to exert other biological functions (in autism and depression) far beyond the gut. Moreover, studies conducted on the regulation of 5-HT in the immune system demonstrated that 5-HT exerts anti-inflammatory and proinflammatory effects on the gut by binding to different receptors under intestinal inflammatory conditions. Understanding the regulatory mechanisms through which 5-HT participates in cell metabolism and physiology can provide potential therapeutic strategies for treating intestinal diseases. Herein, we review recent evidence to recapitulate the mechanisms of synthesis, secretion, regulation, and biofunction of 5-HT to improve the nutrition and health of humans.
Highlights
Serotonin, or 5-Hydroxytryptamine (5-HT), a metabolite of tryptophan (Trp), is an important gastrointestinal (GI) regulatory factor with a wide range of physiological effects on humans and animals [1,2,3,4]
Once 5-HT is released into the lamina propria, it is taken up by the epithelial cells through the serotonin reuptake transporter (SERT)
The low glucose availability leads to the upregulation of glucose transporter 1 (GLUT1), which is a high-affinity and low-capacity glucose transporter
Summary
5-Hydroxytryptamine (5-HT), a metabolite of tryptophan (Trp), is an important gastrointestinal (GI) regulatory factor with a wide range of physiological effects on humans and animals [1,2,3,4]. The physiological effects of 5-HT have been considerably investigated, and 5-HT has been reported to play a crucial role in GI regulation, in intestinal motility and secretion [2]. Serotonin has been shown to exert anti-inflammatory and proinflammatory effects on the gut by binding to different 5-HT receptors in animal models of inflammatory bowel disease (IBD) and colitis [8]. New clues have demonstrated that 5-HT exerts an anti-inflammatory effect on the gut by regulating the expression of the 5-HT4 receptor, with beneficial effects on intestinal epithelial cell barrier functions [4]. We provide an in-depth review highlighting the understanding of various factors (gut microbiota, nutrition, and hormones) in the regulation of 5-HT secretion.
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