Tryptophan catabolism in females with irritable bowel syndrome: relationship to interferon-gamma, severity of symptoms and psychiatric co-morbidity

Typeset version

 

TY  - JOUR
  - Fitzgerald, P,Eugene, MC,Clarke, G,Scully, P,Barry, S,Eamonn, MMQ,Shanahan, F,Cryan, J,Timothy, GD
  - 2008
  - August
  - Neurogastroenterology and Motility
  - Tryptophan catabolism in females with irritable bowel syndrome: relationship to interferon-gamma, severity of symptoms and psychiatric co-morbidity
  - Validated
  - ()
  - indoleamine 2 3-dioxygenase interferon-gamma irritable bowel syndrome psychiatric co-morbidity tryptophan catabolism KYNURENINE PATHWAY IMMUNE ACTIVATION MAJOR DEPRESSION MYENTERIC PLEXUS PRIMARY-CARE IFN-GAMMA DEPLETION SEROTONIN RECEPTORS DISORDER
  - 20
  - 1291
  - 1297
  - Irritable bowel syndrome (IBS) has been linked with abnormal serotonin functioning and immune activation. Tryptophan forms the substrate for serotonin biosynthesis, but it can alternatively be catabolized to kynurenine (Kyn) by the enzyme indoleamine 2,3-dioxygenase (IDO), the main inducer of which is interferon-gamma. The primary aim of this study was to test the hypothesis that IBS is associated with increased tryptophan (Trp) catabolism along the Kyn pathway due to increased IFN-gamma levels. Plasma Kyn, Trp and IFN-gamma levels were measured in 41 female IBS subjects and 33 controls. Indoleamine 2,3-dioxygenase activity was assessed using the Kyn to Trp ratio. Psychiatric co-morbidity was assessed using the Patient Health Questionnaire, and severity of IBS assessed using self-report ordinal scales. Irritable bowel syndrome subjects had increased Kyn concentrations compared with controls (P = 0.039) and there was a trend for Kyn:Trp to be increased in the IBS group (P = 0.09). There was a positive correlation between IBS severity and Kyn:Trp (r = 0.57, P < 0.001). Those with severe IBS symptoms had increased Kyn:Trp (P < 0.005) compared to those with less severe symptoms and controls, and were over twice as likely to have depression or anxiety compared to those with less severe IBS (RR = 2.2, 95% CI 1.2-3.9). No difference in IFN-gamma levels was observed between groups; however, IFN-gamma was positively correlated with Kyn:Trp in IBS (r = 0.58, P = 0.005) but not controls (r = 0.12, P = 0.5). Females with IBS have abnormal Trp catabolism. The Kyn:Trp is related to symptom severity, and those with severe IBS symptoms have increased shunting of Trp along the Kyn pathway which contributes to the abnormal serotonergic functioning in this syndrome.
  - DOI 10.1111/j.1365-2982.2008.01195.x
DA  - 2008/08
ER  - 
@article{V43335034,
   = {Fitzgerald,  P and Eugene,  MC and Clarke,  G and Scully,  P and Barry,  S and Eamonn,  MMQ and Shanahan,  F and Cryan,  J and Timothy,  GD },
   = {2008},
   = {August},
   = {Neurogastroenterology and Motility},
   = {Tryptophan catabolism in females with irritable bowel syndrome: relationship to interferon-gamma, severity of symptoms and psychiatric co-morbidity},
   = {Validated},
   = {()},
   = {indoleamine 2 3-dioxygenase interferon-gamma irritable bowel syndrome psychiatric co-morbidity tryptophan catabolism KYNURENINE PATHWAY IMMUNE ACTIVATION MAJOR DEPRESSION MYENTERIC PLEXUS PRIMARY-CARE IFN-GAMMA DEPLETION SEROTONIN RECEPTORS DISORDER},
   = {20},
  pages = {1291--1297},
   = {{Irritable bowel syndrome (IBS) has been linked with abnormal serotonin functioning and immune activation. Tryptophan forms the substrate for serotonin biosynthesis, but it can alternatively be catabolized to kynurenine (Kyn) by the enzyme indoleamine 2,3-dioxygenase (IDO), the main inducer of which is interferon-gamma. The primary aim of this study was to test the hypothesis that IBS is associated with increased tryptophan (Trp) catabolism along the Kyn pathway due to increased IFN-gamma levels. Plasma Kyn, Trp and IFN-gamma levels were measured in 41 female IBS subjects and 33 controls. Indoleamine 2,3-dioxygenase activity was assessed using the Kyn to Trp ratio. Psychiatric co-morbidity was assessed using the Patient Health Questionnaire, and severity of IBS assessed using self-report ordinal scales. Irritable bowel syndrome subjects had increased Kyn concentrations compared with controls (P = 0.039) and there was a trend for Kyn:Trp to be increased in the IBS group (P = 0.09). There was a positive correlation between IBS severity and Kyn:Trp (r = 0.57, P < 0.001). Those with severe IBS symptoms had increased Kyn:Trp (P < 0.005) compared to those with less severe symptoms and controls, and were over twice as likely to have depression or anxiety compared to those with less severe IBS (RR = 2.2, 95% CI 1.2-3.9). No difference in IFN-gamma levels was observed between groups; however, IFN-gamma was positively correlated with Kyn:Trp in IBS (r = 0.58, P = 0.005) but not controls (r = 0.12, P = 0.5). Females with IBS have abnormal Trp catabolism. The Kyn:Trp is related to symptom severity, and those with severe IBS symptoms have increased shunting of Trp along the Kyn pathway which contributes to the abnormal serotonergic functioning in this syndrome.}},
   = {DOI 10.1111/j.1365-2982.2008.01195.x},
  source = {IRIS}
}
AUTHORSFitzgerald, P,Eugene, MC,Clarke, G,Scully, P,Barry, S,Eamonn, MMQ,Shanahan, F,Cryan, J,Timothy, GD
YEAR2008
MONTHAugust
JOURNAL_CODENeurogastroenterology and Motility
TITLETryptophan catabolism in females with irritable bowel syndrome: relationship to interferon-gamma, severity of symptoms and psychiatric co-morbidity
STATUSValidated
TIMES_CITED()
SEARCH_KEYWORDindoleamine 2 3-dioxygenase interferon-gamma irritable bowel syndrome psychiatric co-morbidity tryptophan catabolism KYNURENINE PATHWAY IMMUNE ACTIVATION MAJOR DEPRESSION MYENTERIC PLEXUS PRIMARY-CARE IFN-GAMMA DEPLETION SEROTONIN RECEPTORS DISORDER
VOLUME20
ISSUE
START_PAGE1291
END_PAGE1297
ABSTRACTIrritable bowel syndrome (IBS) has been linked with abnormal serotonin functioning and immune activation. Tryptophan forms the substrate for serotonin biosynthesis, but it can alternatively be catabolized to kynurenine (Kyn) by the enzyme indoleamine 2,3-dioxygenase (IDO), the main inducer of which is interferon-gamma. The primary aim of this study was to test the hypothesis that IBS is associated with increased tryptophan (Trp) catabolism along the Kyn pathway due to increased IFN-gamma levels. Plasma Kyn, Trp and IFN-gamma levels were measured in 41 female IBS subjects and 33 controls. Indoleamine 2,3-dioxygenase activity was assessed using the Kyn to Trp ratio. Psychiatric co-morbidity was assessed using the Patient Health Questionnaire, and severity of IBS assessed using self-report ordinal scales. Irritable bowel syndrome subjects had increased Kyn concentrations compared with controls (P = 0.039) and there was a trend for Kyn:Trp to be increased in the IBS group (P = 0.09). There was a positive correlation between IBS severity and Kyn:Trp (r = 0.57, P < 0.001). Those with severe IBS symptoms had increased Kyn:Trp (P < 0.005) compared to those with less severe symptoms and controls, and were over twice as likely to have depression or anxiety compared to those with less severe IBS (RR = 2.2, 95% CI 1.2-3.9). No difference in IFN-gamma levels was observed between groups; however, IFN-gamma was positively correlated with Kyn:Trp in IBS (r = 0.58, P = 0.005) but not controls (r = 0.12, P = 0.5). Females with IBS have abnormal Trp catabolism. The Kyn:Trp is related to symptom severity, and those with severe IBS symptoms have increased shunting of Trp along the Kyn pathway which contributes to the abnormal serotonergic functioning in this syndrome.
PUBLISHER_LOCATION
ISBN_ISSN
EDITION
URL
DOI_LINKDOI 10.1111/j.1365-2982.2008.01195.x
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