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. 2025 Oct 28;44(10):116434.
doi: 10.1016/j.celrep.2025.116434. Epub 2025 Oct 20.

Identification of human gut bacteria that produce bioactive serotonin and promote colonic innervation

Chiara H Moretti  1 , Estelle Grasset  1 , Jiaying Zhu  1 , Gaohua Yang  1 , Louise E Olofsson  1 , Muhammad Tanweer Khan  2 , Per-Olof Bergh  1 , Jee-Hwan Oh  3 , Annika Lundqvist  1 , Tom van Gils  1 , Manuela Krämer  1 , Lisa M Olsson  1 , Piyush Patel  1 , Matthias Mitteregger  1 , Daysi Espinola Monges  1 , Chinmay Dwibedi  4 , Kimberly A Krautkramer  1 , Nienke Koopman  1 , Marcus Henricsson  1 , Andrew J Macpherson  5 , Thue Schwartz  6 , Gianfranco Grompone  2 , Jan-Peter van Pijkeren  3 , Valentina Tremaroli  1 , Stefan Roos  7 , Magnus Simrén  1 , Fredrik Bäckhed  8
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Free article

Identification of human gut bacteria that produce bioactive serotonin and promote colonic innervation

Chiara H Moretti et al. Cell Rep. .
Free article

Abstract

The gut microbiota regulates host intestinal serotonin synthesis, thereby promoting the development and maintenance of the enteric nervous system, which controls bowel motility. Functional bowel disorders, including irritable bowel syndrome, are associated with altered serotonin levels and gut microbiota composition. However, it is unclear if the gut microbiota can synthesize bioactive serotonin, which may affect enteric nervous system development. Here, we identify a consortium of the human gut bacteria Limosilactobacillus mucosae and Ligilactobacillus ruminis that synthesizes serotonin in vitro by decarboxylation of 5-hydroxytryptophan and elevates fecal serotonin levels, colonic neuronal density, and serotonin-immunoreactive neurons when introduced into germ-free, serotonin-deficient mice. The consortium normalizes intestinal transit time in germ-free wild-type mice, and we observe decreased fecal abundance of L. mucosae in individuals with irritable bowel syndrome. These findings suggest that specific members of the human gut microbiota synthesize bioactive serotonin that can contribute to gut health.

Keywords: CP: Microbiology; enteric nervous system; gut microbiota; irritable bowel syndrome; lactobacilli; serotonin; tryptophan.

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Conflict of interest statement

Declaration of interests M.T.K., G.G., and S.R. are employed or in part employed by BioGaia AB. L.M.O., M.T.K., and V.T. are co-founders and shareholders of Roxbiosens Inc. J.-P.v.P. receives research funding from BioGaia AB and is the founder and owner of Next-Gen Probiotics, LLC, a consulting company. F.B. receives research funding from BioGaia AB and Novo Nordisk A/S and is the co-founder and a shareholder of Roxbiosens Inc and Implexion AB. M.S. receives research funding from BioGaia AB and has been a consultant/advisory board member for Biocodex, Tillotts, BioGaia, Renapharma, and AlfaSigma and on the speaker’s bureau for Tillotts, Takeda, Biocodex, Sanofi, Abbvie, Janssen Immunology, Pfizer, BioGaia, Renapharma, Mayoly, and Bromatech. However, these possible conflicts of interest have no direct relations to the content of the current paper. A patent application based on the findings has been submitted.

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