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Open Access Research article

Tryptophan degradation in irritable bowel syndrome: evidence of indoleamine 2,3-dioxygenase activation in a male cohort

Gerard Clarke12*, Peter Fitzgerald12, John F Cryan23, Eugene M Cassidy1, Eamonn M Quigley24 and Timothy G Dinan12

  • * Corresponding author: Gerard Clarke g.clarke@ucc.ie

  • † Equal contributors

Author Affiliations

1 Department of Psychiatry, University College Cork, Cork, Ireland

2 Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland

3 Department of Pharmacology & Therapeutics, University College Cork, Cork, Ireland

4 Department of Medicine, University College Cork, Cork, Ireland

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BMC Gastroenterology 2009, 9:6  doi:10.1186/1471-230X-9-6

Published: 20 January 2009

Abstract

Background

Irritable bowel syndrome (IBS) is a common disorder that affects 10–15% of the population. Although characterised by a lack of reliable biological markers, the disease state is increasingly viewed as a disorder of the brain-gut axis. In particular, accumulating evidence points to the involvement of both the central and peripheral serotonergic systems in disease symptomatology. Furthermore, altered tryptophan metabolism and indoleamine 2,3-dioxygenase (IDO) activity are hallmarks of many stress-related disorders. The kynurenine pathway of tryptophan degradation may serve to link these findings to the low level immune activation recently described in IBS. In this study, we investigated tryptophan degradation in a male IBS cohort (n = 10) and control subjects (n = 26).

Methods

Plasma samples were obtained from patients and healthy controls. Tryptophan and its metabolites were measured by high performance liquid chromatography (HPLC) and neopterin, a sensitive marker of immune activation, was measured using a commercially available ELISA assay.

Results

Both kynurenine levels and the kynurenine:tryptophan ratio were significantly increased in the IBS cohort compared with healthy controls. Neopterin was also increased in the IBS subjects and the concentration of the neuroprotective metabolite kynurenic acid was decreased, as was the kynurenic acid:kynurenine ratio.

Conclusion

These findings suggest that the activity of IDO, the immunoresponsive enzyme which is responsible for the degradation of tryptophan along this pathway, is enhanced in IBS patients relative to controls. This study provides novel evidence for an immune-mediated degradation of tryptophan in a male IBS population and identifies the kynurenine pathway as a potential source of biomarkers in this debilitating condition.