Tryptophan (TRP) metabolism could occur both peripherally and centrally, which plays an essential role in brain and gastrointestinal disorders. The participation of TRP metabolism in the bidirectional brain-gut interactions is of value to better understand the mechanism of the pathophysiology of depression. To compare the difference between peripheral and cerebral TRP metabolism in depression, the chronic unpredicted mild stress (CUMS) was used to induce depressive-like syndrome in rats. After the rats were subjected to CUMS for five weeks, TRP and its metabolites were determined by prominence ultrafast liquid chromatography (UFLC) coupled with a QTRAP 5500 mass spectrometer (UFLC-QTRAP-5500/MS), and the expression of TRP metabolic enzymes were examined by Real-time quantitative PCR (qRT-PCR). CUMS induced TRP metabolism abnormalities in the colon, cortex and hippocampus of rats. There were regional metabolism differences, but the common points were the upregulation of indoleamine-2,3-dioxygenase 1 (IDO1) and the increased contents of Kynurenine (KYN), which suggested that KYN pathway (KP) was more favored than the serotonin (5-HT) pathway in the TRP metabolism under CUMS in the three regions studied. More importantly, KYN was preferentially metabolized into neurotoxic 3-hydroxycaninuric acid (3-HK) branch in the cortex and hippocampus while Kynurenic acid (KA) branch in the colon under CUMS. Interestingly, according to the Pearson's correlation coefficients, there may be correlations between the colonic KYN and cerebral 3-HK and KA. It advances our understanding of the role of TRP metabolism in gut-brain communication and provides new research ideas and methods for depression.

色氨酸 (TRP) 代谢可以发生在外周和中枢，这在大脑和胃肠道疾病中起着重要作用。TRP 代谢参与脑-肠双向相互作用对于更好地了解抑郁症的病理生理机制具有重要意义。为了比较抑郁症中外周和大脑 TRP 代谢的差异，慢性不可预测的轻度应激 (CUMS) 用于诱导大鼠抑郁样综合征。大鼠进行CUMS 5周后，采用超快液相色谱（UFLC）联用QTRAP 5500质谱仪（UFLC-QTRAP-5500/MS）测定TRP及其代谢物，TRP代谢酶的表达为通过实时定量 PCR (qRT-PCR) 检查。CUMS 诱导结肠中的 TRP 代谢异常，大鼠的皮层和海马体。存在区域代谢差异，但共同点是吲哚胺-2,3-双加氧酶1（IDO1）的上调和犬尿氨酸（KYN）的含量增加，这表明KYN途径（KP）比5-羟色胺更受青睐。 5-HT) 途径在三个研究区域的 CUMS 下 TRP 代谢。更重要的是，在 CUMS 下，KYN 优先代谢为皮质和海马中具有神经毒性的 3-羟基犬尿酸 (3-HK) 分支，而犬尿酸 (KA) 在结肠中分支。有趣的是，根据 Pearson 相关系数，结肠 KYN 与大脑 3-HK 和 KA 之间可能存在相关性。它促进了我们对 TRP 代谢在肠脑交流中作用的理解，并为抑郁症提供了新的研究思路和方法。