必需氨基酸色氨酸的几种代谢物已通过不同的细胞途径，特别是通过可以激活芳基碳氢化合物受体（AHR）的代谢物，成为肠道稳态的关键参与者。本研究旨在绘制生命早期色氨酸的代谢图，并研究特定代谢物对上皮细胞和屏障完整性的影响。在足月和早产新生儿的粪便以及人乳和配方奶粉中检测到了 21 种色氨酸代谢物。在 Caco2 细胞和人胎儿类器官 (HFO) 中评估了特定 AHR 代谢物调节细胞因子诱导的 IL8 表达和维持屏障完整性的能力。总体而言，与早产儿相比，足月新生儿粪便中色氨酸代谢物的浓度更高。在 AHR 代谢物中，足月新生儿粪便中的吲哚-3-乳酸 (ILA) 显着较高。与配方奶相比，母乳中含有不同水平的几种色氨酸代谢物。特别是，在 AHR 代谢物中，3-吲哚硫酸盐 (I3S) 和 3-吲哚乙酸 (IAA) 明显高于配方奶粉。粪便来源的 ILA 和牛奶来源的 IAA 能够以 AHR 依赖性方式减少 Caco2 细胞和 HFO 中 TNFα 诱导的 IL8 表达。此外，粪便来源的 ILA 和牛奶来源的 IAA 显着减少了 TNFα 诱导的 HFO 屏障破坏。

Several metabolites of the essential amino acid tryptophan have emerged as key players in gut homeostasis through different cellular pathways, particularly through metabolites which can activate the aryl hydrocarbon receptor (AHR). This study aimed to map the metabolism of tryptophan in early life and investigate the effects of specific metabolites on epithelial cells and barrier integrity. Twenty-one tryptophan metabolites were measured in the feces of full-term and preterm neonates as well as in human milk and formula. The ability of specific AHR metabolites to regulate cytokine-induced IL8 expression and maintain barrier integrity was assessed in Caco2 cells and human fetal organoids (HFOs). Overall, higher concentrations of tryptophan metabolites were measured in the feces of full-term neonates compared to those of preterm ones. Within AHR metabolites, indole-3-lactic acid (ILA) was significantly higher in the feces of full-term neonates. Human milk contained different levels of several tryptophan metabolites compared to formula. Particularly, within the AHR metabolites, indole-3-sulfate (I3S) and indole-3-acetic acid (IAA) were significantly higher compared to formula. Fecal-derived ILA and milk-derived IAA were capable of reducing TNFα-induced IL8 expression in Caco2 cells and HFOs in an AHR-dependent manner. Furthermore, fecal-derived ILA and milk-derived IAA significantly reduced TNFα-induced barrier disruption in HFOs.