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


METHODS
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.
Top Institute Food and Nutrition, Wageningen, Netherlands. daniel.keszthelyi@maastrichtuniversity.nl
Daniel
D
Keszthelyi
Freddy J
FJ
Troost
Daisy M
DM
Jonkers
Eva L
EL
van Donkelaar
Jan
J
Dekker
Wim A
WA
Buurman
Ad A
AA
Masclee
D000328:Adult; D002490:Central Nervous System / Q000187:drug effects / Q000378:metabolism; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000097:blood / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000187:drug effects*; D007736:Kynurenic Acid / Q000378:metabolism; D007737:Kynurenine / Q000378:metabolism; D008297:Male; D012701:Serotonin / Q000097:blood / Q000378:metabolism*; D014364:Tryptophan / Q000172:deficiency*; D055815:Young Adult
D012701:Serotonin; D007737:Kynurenine; D006897:Hydroxyindoleacetic Acid; D014364:Tryptophan; D007736:Kynurenic Acid