Does acute tryptophan depletion affect peripheral serotonin metabolism in the intestine?123

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Background: 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.

Objective: 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.

Design: 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.

Results: 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.

Conclusions: 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.

Abbreviations:

ATD
acute tryptophan depletion
CNS
central nervous system
EC
enterochromaffin cell
HAM-D17
17-item Hamilton Depression Rating Scale
HPLC-MS
HPLC–mass spectrometry
KA
kynurenic acid
MUMC
Maastricht University Medical Centre+
SCL-90
Dutch version of the symptom checklist
5-HIAA
5-hydroxyindoleacetic acid
5-HT
5-hydroxytryptamine.

Cited by (0)

1

From the Top Institute Food and Nutrition, Wageningen, Netherlands (DK, FJT, DMJ, JD, and AAM); the Division of Gastroenterology-Hepatology, Department of Internal Medicine, Maastricht University Medical Centre+, Maastricht, Netherlands (DK, FJT, DMJ, and AAM); the Department of Psychiatry and Neuropsychology, Faculty of Health, Medicine and Life Sciences, School for Mental Health and Neuroscience, Maastricht University, Maastricht, Netherlands (EvD); the Department of Surgery, Maastricht University Medical Centre+, Maastricht, Netherlands (WAB); and the Department of Animal Sciences, Wageningen University, Wageningen, Netherlands (JD).

2

Supported by NIH grant 1R01DK079913.

3

Address correspondence and reprint requests to D Keszthelyi, Department of Internal Medicine, Division of Gastroenterology-Hepatology, Maastricht University Medical Center, PO Box 5800, 6202 AZ Maastricht, Netherlands. E-mail: [email protected]