Measurement of real-time serotonin dynamics from human-derived gut organoids
File(s)
Author(s)
Bohl, Bettina
Lei, Yuxian
Bewick, Gavin A
Hashemi, Parastoo
Type
Journal Article
Abstract
The importance of the gut in regulating the brain–body immune axis is becoming increasingly evident. Interestingly, the brain and gut share many common signaling molecules, with serotonin being one of the most notable. In fact, the gut is the primary source of serotonin in the body. However, studying serotonin dynamics in a human-specific context remains a challenge. Human stem cell-derived models provide a promising avenue for studying signal transmission in well-controlled, in vitro environments. In this study, we report the first fast-scan cyclic voltammetry (FSCV) measurements of serotonin signaling in a newly developed enterochromaffin cell (ECC)-enriched gut organoid model. First, we characterize the stem cell-derived gut organoids and confirm they are enriched with ECCs, the key cell type responsible for producing and releasing serotonin in the gut. We then optimize an in vitro buffer that maintains cell viability while supporting FSCV measurements. Using this system, we detect spontaneous release events, which increase in frequency and amplitude following stimulation with forskolin (FSK) and 3-isobutyl-1-methylxanthine (IBMX). Finally, we confirm the identity of the signal as serotonin using a selective serotonin reuptake inhibitor (SSRI), which significantly delayed the reuptake profile. Our study introduces the first real-time measurement of serotonin signaling in a human-derived gut model. We believe this system will be essential for future research on serotonin’s role in the gut and for potential novel drug target identification.
Date Issued
2025-03-11
Date Acceptance
2025-02-04
Citation
Analytical Chemistry, 2025, 97 (9), pp.5057-5065
ISSN
0003-2700
Publisher
American Chemical Society
Start Page
5057
End Page
5065
Journal / Book Title
Analytical Chemistry
Volume
97
Issue
9
Copyright Statement
© 2025 The Authors. Published by American Chemical Society. This publication is licensed under CC-BY 4.0
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/40007472
Subjects
ANTIDEPRESSANTS
BRAIN
Chemistry
Chemistry, Analytical
CYCLIC-AMP
Physical Sciences
Science & Technology
SECRETION
TRANSPORTER
Publication Status
Published
Coverage Spatial
United States
Date Publish Online
2025-02-26