Serotonin (also known as 5-hydroxytryptamine or 5-HT) controls gut motility, platelet function, mood regulation and has been implicated in inflammatory bowel disease, but its role in the neonatal gut is unclear. In Science Immunology, Sanidad et al. find that 5-HT derived from the microbiota promotes the differentiation of regulatory T (Treg) cells and confers tolerance to dietary antigens and commensal bacteria. Metabolomic analysis of mice showed that 5-HT levels were increased in the neonatal small intestine compared with the small intestine of adult mice, whereas there was no increase in 5-HT levels in germ-free (GF) neonatal mice. Expression of the rate-limiting enzyme involved in 5-HT biosynthesis was increased in neonatal small intestine from specific pathogen-free (SPF) mice compared with GF mice, and this was restored by recolonization of GF mice with bacterial isolates. Bacteria isolated from mouse and human neonatal intestines produced 5-HT in vitro. When GF mice were supplemented with 5-HT, there was an increase in the number of Treg cells in the small intestine. T cells stimulated with 5-HT ex vivo had reduced mTOR pathway activation compared with controls. The treatment of GF neonates with 5-HT in an oral tolerance model resulted in lower ovalbumin (OVA)-specific antibodies after OVA sensitization, and more Treg cells in the small intestine compared to controls. After the adoptive transfer of naive T cells from 5-HT-treated or control mice to Rag2−/− recipient mice, the recipients with T cells from 5-HT-treated donors had reduced gut inflammation. Together, this suggest that 5-HT derived from neonatal gut microbiota shapes the Treg cell response to dietary antigens and commensal bacteria.
Original reference: Sci. Immunol. 9, eadj4775 (2024)
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