Serotonergic reinforcement of intestinal barrier function is impaired in irritable bowel syndrome

Authors

  • D. Keszthelyi,

    Corresponding author
    1. Top Institute Food and Nutrition, Wageningen, The Netherlands
    2. Division of Gastroenterology-Hepatology, Department of Internal Medicine, Maastricht University Medical Centre+, Maastricht, The Netherlands
    • Correspondence to:

      Dr D. Keszthelyi, Division of Gastroenterology-Hepatology, Department of Internal Medicine, Maastricht University Medical Centre+, PO Box 5800, 6202 AZ Maastricht, The Netherlands.

      E-mail: daniel.keszthelyi@maastrichtuniversity.nl

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  • F. J. Troost,

    1. Top Institute Food and Nutrition, Wageningen, The Netherlands
    2. Division of Gastroenterology-Hepatology, Department of Internal Medicine, Maastricht University Medical Centre+, Maastricht, The Netherlands
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  • D. M. Jonkers,

    1. Top Institute Food and Nutrition, Wageningen, The Netherlands
    2. Division of Gastroenterology-Hepatology, Department of Internal Medicine, Maastricht University Medical Centre+, Maastricht, The Netherlands
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  • H. M. van Eijk,

    1. Department of Surgery, Maastricht University Medical Centre+, Maastricht, The Netherlands
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  • P. J. Lindsey,

    1. Department of Clinical Genetics and Bioinformatics, Maastricht University Medical Centre+, Maastricht, The Netherlands
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  • J. Dekker,

    1. Top Institute Food and Nutrition, Wageningen, The Netherlands
    2. Host-Microbe Interomics Group, Department of Animal Sciences, Wageningen University, Wageningen, The Netherlands
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  • W. A. Buurman,

    1. School for Mental Health and Neurosciences, Maastricht University Medical Center+, Maastricht, The Netherlands
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  • A. A. M. Masclee

    1. Top Institute Food and Nutrition, Wageningen, The Netherlands
    2. Division of Gastroenterology-Hepatology, Department of Internal Medicine, Maastricht University Medical Centre+, Maastricht, The Netherlands
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  • This article was accepted for publication after full peer-review.

Summary

Background

Alterations in serotonergic (5-HT) metabolism and/or intestinal integrity have been associated with irritable bowel syndrome (IBS).

Aims

To assess the effects of the precursor of 5-HT, 5-hydroxytryptophan (5-HTP), on mucosal 5-HT availability and intestinal integrity, and to assess potential differences between healthy controls and IBS patients.

Methods

Fifteen IBS patients and 15 healthy volunteers participated in this randomised double-blind placebo-controlled study. Intestinal integrity was assessed by dual-sugar test and by determining the mucosal expression of tight junction proteins after ingestion of an oral bolus of 100 mg 5-HTP or placebo. Mucosal serotonergic metabolism was assessed in duodenal biopsy samples.

Results

5-HTP administration significantly increased mucosal levels of 5-HIAA, the main metabolite of 5-HT, in both healthy controls (7.1 ± 1.7 vs. 2.5 ± 0.7 pmol/mg, 5-HTP vs. placebo, = 0.02) and IBS patients (20.0 ± 4.8 vs. 8.1 ± 1.3 pmol/mg, 5-HTP vs. placebo, P = 0.02), with the latter group showing a significantly larger increase. Lactulose/L-rhamnose ratios were significantly lower after administration of 5-HTP (P < 0.05) in healthy controls and were accompanied by redistribution of zonula occludens-1 (ZO-1), pointing to reinforcement of the barrier. In IBS, expression of the tight junction proteins was significantly lower compared to healthy controls, and 5-HTP resulted in a further decrease in occludin expression.

Conclusions

Oral 5-HTP induced alterations in mucosal 5-HT metabolism. In healthy controls, a reinforcement of the intestinal barrier was seen whereas such reaction was absent in IBS patients. This could indicate the presence of a serotonin-mediated mechanism aimed to reinforce intestinal barrier function, which seems to dysfunction in IBS patients.

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