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.

中文翻译：

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肠道细菌衍生的血清素可促进生命早期的免疫耐受

肠道微生物群促进生命早期免疫系统的发育，但肠道代谢组与新生儿肠道免疫细胞之间的相互作用在很大程度上仍不清楚。在这里，我们证明新生儿肠道富含包括血清素在内的神经递质，并且特定的肠道细菌直接产生血清素，同时下调单胺氧化酶 A 以限制血清素分解。我们发现，血清素直接向 T 细胞发出信号，增加细胞内 indole-3-acetaldehdye 并抑制 mTOR 激活，从而促进新生儿肠道离体和体内调节性 T 细胞的分化。给新生小鼠口服血清素可产生针对饮食抗原和共生细菌的长期 T 细胞介导的抗原特异性免疫耐受。总之，我们的研究发现了特定肠道细菌在增加新生儿肠道中血清素可用性方面的重要作用，并确定了肠道血清素在塑造 T 细胞对饮食抗原和共生细菌的反应以促进生命早期免疫耐受方面的功能。