Serotonin Deficiency Is Associated With Delayed Gastric Emptying

Lai Wei, Rajan Singh, Se Eun Ha, Alyce M. Martin, Lauren A. Jones, Byungchang Jin, Brian G. Jorgensen, Hannah Zogg, Tyler Chervo, Andres Gottfried-Blackmore, Linda Nguyen, Aida Habtezion, Nick J. Spencer, Damien J. Keating, Kenton M. Sanders, Seungil Ro

Research output: Contribution to journalArticlepeer-review

43 Citations (Scopus)


Background & Aims: Gastrointestinal (GI) motility is regulated by serotonin (5-hydroxytryptamine [5-HT]), which is primarily produced by enterochromaffin (EC) cells in the GI tract. However, the precise roles of EC cell-derived 5-HT in regulating gastric motility remain a major point of conjecture. Using a novel transgenic mouse line, we investigated the distribution of EC cells and the pathophysiologic roles of 5-HT deficiency in gastric motility in mice and humans. Methods: We developed an inducible, EC cell–specific Tph1CreERT2/+ mouse, which was used to generate a reporter mouse line, Tph1-tdTom, and an EC cell–depleted line, Tph1-DTA. We examined EC cell distribution, morphology, and subpopulations in reporter mice. GI motility was measured in vivo and ex vivo in EC cell–depleted mice. Additionally, we evaluated 5-HT content in biopsy and plasma specimens from patients with idiopathic gastroparesis (IG). Results: Tph1-tdTom mice showed EC cells that were heterogeneously distributed throughout the GI tract with the greatest abundance in the antrum and proximal colon. Two subpopulations of EC cells were identified in the gut: self-renewal cells located at the base of the crypt and mature cells observed in the villi. Tph1-DTA mice displayed delayed gastric emptying, total GI transit, and colonic transit. These gut motility alterations were reversed by exogenous provision of 5-HT. Patients with IG had a significant reduction of antral EC cell numbers and 5-HT content, which negatively correlated with gastric emptying rate. Conclusions: The Tph1CreERT2/+ mouse provides a powerful tool to study the functional roles of EC cells in the GI tract. Our findings suggest a new pathophysiologic mechanism of 5-HT deficiency in IG.

Original languageEnglish
Pages (from-to)2451-2466.e19
Number of pages35
Issue number7
Early online date2 Mar 2021
Publication statusPublished - Jun 2021


  • Enterochromaffin Cells
  • Gastrointestinal Motility
  • Idiopathic Gastroparesis
  • Serotonin
  • Slow-Transit Constipation


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