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. 2023 Jul 13;7(1):88–96. doi: 10.1093/jcag/gwad020

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© The Author(s) 2023. Published by Oxford University Press on behalf of the Canadian Association of Gastroenterology.

This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

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Figure 1. — Gut-derived serotonin (5-HT) and its impact in the gut. In enterochromaffin (EC) cells, dietary tryptophan is converted by the rate-limiting enzyme tryptophan hydroxylase 1 (TPH1) to 5-hydroxytryptophan or 5-HTP. 5-HTP is then converted by aromatic amino acid decarboxylase (AADC) to serotonin or 5-hydroxytryptamine (5-HT). 5-HT is then sequestered by vesicular monoamine transport 1 (VMAT1) into storage vesicles at the basolateral membrane of the enterochromaffin (EC) cell until primed for release. Upon release by exocytosis, 5-HT can, in neighbouring enterocytes or neurons, interact via several receptors found in the gut, be taken up by the serotonin transporter, where it can be broken down, or contribute to post-translational modifications via serotonylation (1). 5-HT may also be taken up by platelets and distributed to various sites around the body, where it can elicit numerous physiological effects (2). 5-HT can also directly affect local immune cell activity and proliferation (3), and impact the composition and function of gut microbes (4).