Top Institute Food and Nutrition, Wageningen, Netherlands.
Am J Clin Nutr. 2012 Mar;95(3):603-8. doi: 10.3945/ajcn.111.028589. Epub 2012 Feb 1.
Serotonin (5-hydroxytryptamine; 5-HT), a tryptophan metabolite, plays an important regulatory role in the human central nervous system and in the gastrointestinal tract. Acute tryptophan depletion (ATD) is currently the most widely established method to investigate 5-HT metabolism.
The aim of this study was to assess the effect of an acute decrease in the systemic availability of tryptophan on intestinal 5-HT metabolism and permeability.
Thirty-three healthy volunteers (17 with ATD, 3 of whom dropped out; 16 placebo) participated in this randomized placebo-controlled study. Plasma and duodenal mucosal concentrations of 5-HT, 5-hydroxyindoleacetic acid (5-HIAA), and kynurenic acid (KA) were measured by HPLC-mass spectrometry. Intestinal barrier function was assessed with a multisugar plasma test, and analysis of tight junction transcription was performed in duodenal biopsy samples obtained by gastroduodenoscopy.
Mucosal 5-HT, 5-HIAA, and KA concentrations remained unaltered by ATD. In contrast, ATD significantly decreased plasma 5-HT (P < 0.05) and 5-HIAA (P < 0.0001) concentrations. After endoscopy, a significant increase in plasma 5-HT concentrations was observed in the placebo group (P = 0.029) compared with the ATD group. Moreover, a significant increase in plasma KA concentrations over time was found in the placebo group (P < 0.05). No changes in intestinal barrier function were observed.
An acute decrease in precursor availability does not affect mucosal concentrations of serotonergic metabolites, in contrast with systemic concentrations. ATD alters biochemical responses to acute stress from the endoscopic examination reflected by lower 5-HT concentrations. Changes in 5-HT concentrations were paralleled by alterations in KA concentrations, which suggest competition between the 2 metabolic pathways for the mutual precursor. This trial was registered at clinicaltrials.gov as NCT00731003.
血清素（5-羟色胺；5-HT）是色氨酸的代谢产物，在人体中枢神经系统和胃肠道中发挥重要的调节作用。急性色氨酸耗竭（ATD）是目前研究 5-HT 代谢最广泛的方法。
本研究旨在评估系统性色氨酸可用性降低对肠道 5-HT 代谢和通透性的影响。
33 名健康志愿者（17 名接受 ATD，其中 3 名脱落；16 名安慰剂）参加了这项随机安慰剂对照研究。通过 HPLC-质谱法测量血浆和十二指肠黏膜中 5-HT、5-羟吲哚乙酸（5-HIAA）和犬尿氨酸（KA）的浓度。通过多聚糖血浆测试评估肠道屏障功能，并通过胃镜检查获得的十二指肠活检样本分析紧密连接转录。
ATD 对黏膜 5-HT、5-HIAA 和 KA 浓度没有影响。相反，ATD 显著降低了血浆 5-HT（P < 0.05）和 5-HIAA（P < 0.0001）浓度。内镜检查后，安慰剂组血浆 5-HT 浓度显著升高（P = 0.029），与 ATD 组相比。此外，安慰剂组血浆 KA 浓度随时间显著增加（P < 0.05）。未观察到肠道屏障功能的变化。
前体可用性的急性降低不会影响肠黏膜中 5-羟色胺代谢物的浓度，而对系统浓度则有影响。ATD 改变了内镜检查引起的急性应激的生化反应，表现为 5-HT 浓度降低。5-HT 浓度的变化与 KA 浓度的变化平行，这表明两种代谢途径对共同前体存在竞争。这项试验在 clinicaltrials.gov 注册，编号为 NCT00731003。
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