Serotonin Deficiency Is Associated With Delayed Gastric Emptying

Area of Science:

• Gastroenterology
• Cell Biology
• Physiology

Background:

• Gastrointestinal (GI) motility is regulated by serotonin (5-hydroxytryptamine [5-HT]), primarily produced by enterochromaffin (EC) cells.
• The exact role of EC cell-derived 5-HT in gastric motility regulation is not fully understood.

Purpose of the Study:

• To investigate the distribution and function of EC cells.
• To explore the pathophysiological role of 5-HT deficiency in gastric motility.

Main Methods:

• Developed an inducible, EC cell-specific Tph1^CreERT2/+ mouse model (Tph1-tdTom reporter and Tph1-DTA depletion lines).
• Assessed EC cell distribution, morphology, and subpopulations.
• Measured GI motility in vivo and ex vivo.
• Analyzed 5-HT content in biopsy and plasma from idiopathic gastroparesis (IG) patients.

Main Results:

• EC cells are heterogeneously distributed in the GI tract, with two identified subpopulations.
• EC cell depletion in mice led to delayed gastric emptying, GI transit, and colonic transit, reversible with exogenous 5-HT.
• IG patients showed reduced antral EC cell numbers and 5-HT, correlating with impaired gastric emptying.

Conclusions:

• The Tph1^CreERT2/+ mouse is a valuable tool for studying EC cell function.
• Findings suggest a novel pathophysiological mechanism involving 5-HT deficiency in idiopathic gastroparesis.