From the Guidelines
The GI tract plays a crucial role in serotonin production, with approximately 90% of the body's total serotonin being produced in the gut, primarily in enterochromaffin cells, as supported by studies on post-infection irritable bowel syndrome 1. The GI tract's contribution to serotonin production is a complex process involving the synthesis of serotonin from the amino acid tryptophan using the enzyme tryptophan hydroxylase-1 (TPH1) in enterochromaffin cells.
- The production of serotonin in the gut serves multiple local functions, including:
- Regulating intestinal motility
- Controlling secretion
- Modulating sensation
- Gut microbiota also influence serotonin production by interacting with enterochromaffin cells, which can affect mood and digestive function, as noted in studies on the role of peripheral and central factors in the development of irritable bowel syndrome following intestinal infections 1.
- While gut-produced serotonin cannot cross the blood-brain barrier to affect brain function directly, it does enter the bloodstream where it's taken up by platelets and can influence various peripheral functions, including:
- Blood clotting
- Immune responses
- Bone metabolism This gut-brain connection helps explain why digestive disorders often coincide with mood disorders, and why certain medications targeting serotonin can affect both mental health and digestive function, as discussed in the context of post-infection irritable bowel syndrome 1.
From the Research
Role of the GI Tract in Serotonin Production
- The GI tract is the largest producer of serotonin (5-hydroxytryptamine (5-HT)) in the body, with enterochromaffin (EC) cells producing up to 95% of total body serotonin 2.
- EC cells are specialized enteroendocrine cells that coordinate luminal and basolateral communication in the GI tract, affecting gut physiological processes such as motility, absorption, secretion, and chemo/mechanosensation 2.
- The GI tract produces two distinct sources of enteric 5-HT: mucosal 5-HT, predominantly produced by EC cells, and neuronal 5-HT, produced by serotonergic neurons of the enteric nervous system (ENS) 3.
Mechanisms of Serotonin Action in the GI Tract
- Serotonin inhibits gastric acid secretion and may be an endogenous enterogastrone, stimulating the production and release of gastric and colonic mucus 4.
- Serotonin affects neural modulation of gut smooth muscle function and may act either directly on mesenteric vascular smooth muscle or through enteric nerves to influence gastrointestinal blood flow 4.
- Mucosal 5-HT plays an important role in the production of pro-inflammatory mediators from immune cells, while neuronal 5-HT provides neuroprotection in the ENS 3.
Implications for Gut-Brain Interaction and Mood Disorders
- The GI tract modulates emotional behaviors through the action of intestinal epithelial serotonin, which can promote anxiolytic and antidepressive-like effects without causing adverse effects on the GI tract or brain 5.
- Afferent vagal pathways are conduits by which intestinal epithelial serotonin affects behavior, highlighting the importance of the gut-brain axis in mood regulation 5.
- In utero SSRI exposure is a significant and specific risk factor for development of disorders of gut-brain interaction (DGBI), such as functional constipation, in the first year of life 5.