The gut microbiota has a crucial role in immune development in early life. Sanidad et al. show that the mouse neonatal small intestine has a distinct microbiota compared with the adult small intestine and is enriched in neurotransmitters, including serotonin (5-HT). Both human and mouse neonates were found to have an increased abundance of 5-HT-producing bacteria in the small intestine. Gut bacteria in neonates further maximized 5-HT availability by inducing the enzyme TPH1, which promotes the conversion of tryptophan to 5-HT, and by downregulating MAO-A, an enzyme that breaks down 5-HT. In neonates, but not adults, 5-HT directly affected T cell metabolism. In particular, it increased levels of indole-3-acetaldehyde (I3A), which inhibits the mTOR pathway and promotes the development of regulatory T (T_reg) cells. Oral gavage of neonatal (but not adult) mice with 5-HT promoted systemic and lasting antigen-specific immune tolerance to dietary antigens and commensal bacteria. This demonstrates a mechanism by which gut bacteria can promote oral tolerance in early life.

肠道微生物群在生命早期的免疫发育中起着至关重要的作用。萨尼达等人。研究表明，与成人小肠相比，小鼠新生儿小肠具有独特的微生物群，并且富含神经递质，包括血清素 (5-HT)。研究发现，人类和小鼠新生儿的小肠中产生 5-HT 的细菌丰度有所增加。新生儿肠道细菌通过诱导 TPH1 酶（促进色氨酸转化为 5-HT）以及下调 MAO-A（一种分解 5-HT 的酶），进一步最大限度地提高了 5-HT 的利用率。在新生儿中，5-HT 直接影响 T 细胞代谢，但在成人中则不然。特别是，它增加了吲哚-3-乙醛 (I3A) 的水平，从而抑制 mTOR 通路并促进调节性 T (T _reg ) 细胞的发育。对新生（但不是成年）小鼠口服 5-HT 可以促进对饮食抗原和共生细菌的系统性和持久的抗原特异性免疫耐受。这证明了肠道细菌可以促进生命早期口腔耐受性的机制。