Gut bacteria-derived serotonin promotes immune tolerance in early life.

TitleGut bacteria-derived serotonin promotes immune tolerance in early life.
Publication TypeJournal Article
Year of Publication2024
AuthorsSanidad KZ, Rager SL, Carrow HC, Ananthanarayanan A, Callaghan R, Hart LR, Li T, Ravisankar P, Brown JA, Amir M, Jin JC, Savage ARose, Luo R, Rowdo FMardorsky, M Martin L, Silver RB, Guo C-J, Krumsiek J, Inohara N, Zeng MY
JournalSci Immunol
Date Published2024 Mar 15
KeywordsAnimals, Antigens, Bacteria, Gastrointestinal Microbiome, Immune Tolerance, Mice, Serotonin

The gut microbiota promotes immune system development in early life, but the interactions between the gut metabolome and immune cells in the neonatal gut remain largely undefined. Here, we demonstrate that the neonatal gut is uniquely enriched with neurotransmitters, including serotonin, and that specific gut bacteria directly produce serotonin while down-regulating monoamine oxidase A to limit serotonin breakdown. We found that serotonin directly signals to T cells to increase intracellular indole-3-acetaldehdye and inhibit mTOR activation, thereby promoting the differentiation of regulatory T cells, both ex vivo and in vivo in the neonatal intestine. Oral gavage of serotonin into neonatal mice resulted in long-term T cell-mediated antigen-specific immune tolerance toward both dietary antigens and commensal bacteria. Together, our study has uncovered an important role for specific gut bacteria to increase serotonin availability in the neonatal gut and identified a function of gut serotonin in shaping T cell response to dietary antigens and commensal bacteria to promote immune tolerance in early life.

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Alternate JournalSci Immunol
PubMed ID38489352

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