Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Neurotransmitter biosynthesis

A gut feeling

Nature Chemical Biology volume 19, pages 125–126 (2023)Cite this article

Subjects

Unbiased metabolomics revealed the conversion of serotonin into N-acetylserotonin-derived glucosides by an intestinal carboxylesterase in Caenorhabditis elegans, which suggests an unappreciated role of the gut in modulating 5-HT signaling.

Serotonin (5-hydroxytryptamine, 5-HT) was initially identified in the 1930s from gastrointestinal extracts1. Synthesis of 5-HT was later found to also occur in the central nervous system (CNS), as well as in several peripheral tissues. 5-HT interactions with diverse 5-HT receptor subtypes regulate a range of cognitive capabilities, neuropsychological processes and physiological functions2. Metabolism of 5-HT can afford a series of derivatives to enable quick degradation or exert distinct physiological functions3. In addition, systemic 5-HT signaling has been proposed to integrate bidirectional communications between the CNS, gut and enteric microbiota, but the interplay between 5-HT synthesized in different tissues remains unclear4. In this issue of Nature Chemical Biology, Yu et al.5 demonstrate that 5-HT in the nematode C. elegans that originates from neurons and non-neuronal tissues can be converted into a common pool of a new class of derivatives, N-acetylserotonin-derived glucosides, in the gut, where they interface with bacterial indole production. These findings suggest that in addition to deriving from canonical 5-HT signaling, alterations in 5-HT-dependent functions may stem in part from changes in 5-HT glucoside biosynthesis in the gut.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Get just this article for as long as you need it

$39.95

Learn more

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Biosynthesis of serotonin glucosides in C. elegans.

References

  1. Rapport, M. M., Green, A. A. & Page, I. H. Science 108, 329–330 (1948).

    Article  CAS  Google Scholar 

  2. Berger, M., Gray, J. A. & Roth, B. L. Ann. Rev. Med. 60, 355–366 (2009).

    Article  CAS  Google Scholar 

  3. Cipolla-Neto, J. & Amaral, F. G. D. Endocr. Rev. 39, 990–1028 (2018).

    Article  Google Scholar 

  4. Gershon, M. D. & Margolis, K. G. J. Clin. Invest. 131, https://doi.org/10.1172/jci143768 (2021).

  5. Yu, J. et al. Nat. Chem. Biol. https://doi.org/10.1038/s41589-022-01148-7 (2022).

    Article  Google Scholar 

  6. Sze, J. Y., Victor, M., Loer, C., Shi, Y. & Ruvkun, G. Nature 403, 560–564 (2000).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Molecular Pharmacology, Albert Einstein College of Medicine, New York, NY, USA

    Ji Y. Sze

Authors
  1. Ji Y. Sze
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ji Y. Sze.

Ethics declarations

Competing interests

The author declares no competing interests.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Sze, J.Y. A gut feeling. Nat Chem Biol 19, 125–126 (2023). https://doi.org/10.1038/s41589-022-01152-x

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41589-022-01152-x

Search

Advanced search

Quick links

Nature Briefing: Translational Research

Sign up for the Nature Briefing: Translational Research newsletter — top stories in biotechnology, drug discovery and pharma.

Get what matters in translational research, free to your inbox weekly. Sign up for Nature Briefing: Translational Research