Tryptophan Degradation In Irritable Bowel Syndrome: Evidence of Indoleamine 2,3-Dioxygenase Activation In A Male Cohort

Typeset version

 

TY  - JOUR
  - Clarke, G, Fitzgerald, P, Cryan, JF, Cassidy, EM, Quigley, EM, Dinan, TG
  - 2009
  - January
  - BMC Gastroenterology
  - Tryptophan Degradation In Irritable Bowel Syndrome: Evidence of Indoleamine 2,3-Dioxygenase Activation In A Male Cohort
  - Validated
  - ()
  - 9
  - NA
  - 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..
  - DOI 10.1186/1471-230X-9-6
DA  - 2009/01
ER  - 
@article{V721430,
   = {Clarke,  G and  Fitzgerald,  P and  Cryan,  JF and  Cassidy,  EM and  Quigley,  EM and  Dinan,  TG },
   = {2009},
   = {January},
   = {BMC Gastroenterology},
   = {Tryptophan Degradation In Irritable Bowel Syndrome: Evidence of Indoleamine 2,3-Dioxygenase Activation In A Male Cohort},
   = {Validated},
   = {()},
   = {9},
   = {NA},
   = {{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..}},
   = {DOI 10.1186/1471-230X-9-6},
  source = {IRIS}
}
AUTHORSClarke, G, Fitzgerald, P, Cryan, JF, Cassidy, EM, Quigley, EM, Dinan, TG
YEAR2009
MONTHJanuary
JOURNAL_CODEBMC Gastroenterology
TITLETryptophan Degradation In Irritable Bowel Syndrome: Evidence of Indoleamine 2,3-Dioxygenase Activation In A Male Cohort
STATUSValidated
TIMES_CITED()
SEARCH_KEYWORD
VOLUME9
ISSUENA
START_PAGE
END_PAGE
ABSTRACTBackground: 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..
PUBLISHER_LOCATION
ISBN_ISSN
EDITION
URL
DOI_LINKDOI 10.1186/1471-230X-9-6
FUNDING_BODY
GRANT_DETAILS