Is serotonin produced in the gut?

Serotonin Production in the Gut

Yes, approximately 90-95% of the body's serotonin is produced in the gastrointestinal tract, primarily by specialized enterochromaffin (EC) cells. 1

Gut Serotonin Production and Function

• Enterochromaffin cells in the gastrointestinal epithelium are the primary source of serotonin in the body, with only a small portion being produced by neurons in the enteric nervous system 2
• Serotonin (5-hydroxytryptamine or 5-HT) serves as a key signaling molecule in the gut, targeting enterocytes, smooth muscles, and enteric neurons 3
• Gut commensals, particularly spore-forming Clostridiales within the Firmicutes phylum, may help regulate serotonin synthesis in the intestine 4
• Serotonin activates both intrinsic and extrinsic primary afferent neurons to initiate peristaltic and secretory reflexes and transmit information to the central nervous system 3

Separation of Central and Peripheral Serotonin Systems

• The central and peripheral pools of serotonin are anatomically separated as serotonin cannot readily cross the blood-brain barrier 5
• This separation has important clinical implications for disorders of gut-brain interaction, as noted by gastroenterological associations 1
• Despite this separation, the gut and brain communicate through other mechanisms, including neural pathways via the vagus nerve and immune signaling molecules 1

Serotonin Regulation in the Gut

• Serotonin is inactivated by the serotonin reuptake transporter (SERT) in enterocytes or neurons 3
• SERT is located at both apical and basolateral cell membranes of intestinal epithelial cells throughout the jejunum, ileum, and colon 6
• Inhibition of SERT increases the extracellular concentration and transmural transport of serotonin, potentially enhancing physiological responses to this neurotransmitter 6

Clinical Relevance of Gut Serotonin

• Altered serotonin metabolism has been observed in conditions like irritable bowel syndrome (IBS) 1
• Changes in 5-HT metabolism have been detected in patients with post-infectious IBS, with colonic EC cell counts being higher in patients with Campylobacter-associated PI-IBS compared to healthy subjects 4
• In Shigella-associated PI-IBS, both serotonin-containing EC cells and Peptide YY-containing EC cells are increased compared to healthy subjects 4
• Medications targeting serotonin systems, such as tricyclic antidepressants and serotonin-norepinephrine reuptake inhibitors, modulate both central and peripheral pain pathways 1

Physiological Functions of Gut Serotonin

• Serotonin inhibits gastric acid secretion and may function as an endogenous enterogastrone 7
• It stimulates the production and release of gastric and colonic mucus 7
• Serotonin plays important roles in gastrointestinal motility, sensation, inflammation, and neurogenesis 2
• It also functions as a metabolic hormone contributing to glucose homeostasis and adiposity 5

Gut-Brain Axis Communication

• Despite not crossing the blood-brain barrier, serotonin is part of the bidirectional communication system between gut and brain 1
• EC cells act as important luminal sensory cells that can detect and respond to ingested nutrients, gut microbiota, and their associated metabolites 5
• The interaction between gut microbiota and EC cells is dynamic and has significant implications for host physiology 5