Identification of human gut bacteria that produce bioactive serotonin and promote colonic innervation
Chiara H. Moretti, E. Grasset, Jiaying Zhu, Gaohua Yang, Louise E. Olofsson, Muhammad Tanweer Khan, Per-Olof Bergh, Jee‐Hwan Oh, Annika Lundqvist, Tom van Gils, Manuela Krämer, Lisa Olsson, Piyush Patel, Matthias Mitteregger, D. Monges, Chinmay Dwibedi, Kimberly A. Krautkramer, Nienke Koopman, Marcus Henricsson, Andrew J. Macpherson, Thue W. Schwartz, Gianfranco Grompone, Jan-Peter van Pijkeren, Valentina Tremaroli, Stefan Roos, Magnus Simrén, Fredrik Bäckhed
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.