Purine, Kynurenine, Neopterin and Lipid Peroxidation Levels in Inflammatory Bowel Disease

Abstract

The kynurenine metabolites of tryptophan may be involved in the regulation of neuronal activity and thus gut motility and secretion. We have now performed a pilot study to measure serum concentrations of purines and kynurenines in patients with mild inflammatory bowel disease, as well as in sex- and age-matched control subjects. For some analyses, the patients were subdivided into subgroups of those with Crohn’s disease and those with ulcerative colitis. The analyses indicated an increased activity in one branch of the kynurenine pathway. While there was no demonstrable difference in neopterin levels in either of the patient groups compared with controls, indicating that the disorders were in an inactive quiescent phase, both groups showed significantly higher levels of lipid peroxidation products. This suggests the presence of increased oxidative stress even during relative disease inactivity. The increased level of kynurenic acid may represent either a compensatory response to elevated activation of enteric neurones or a primary abnormality which induces a compensatory increase in gut activity. In either case, the data may indicate a role for kynurenine modulation of glutamate receptors in the symptoms of inflammatory bowel disease.

Kynurenine pathway metabolism and the microbiota-gut-brain axis

“…Finally, although not generally considered a brain-gut axis disorder, mood and anxiety problems are common in IBD (Casellas et al, 2002) which may be linked to inflammatory mediated tryptophan metabolism along the kynurenine pathway (Forrest et al, 2003;Forrest et al, 2002). As such there is increasing interest in how dysregulated brain-gut communication impacts on peripheral and central symptoms in IBD (Bernstein et al, 2010;Bonaz and Bernstein, 2013).…”

Kynurenic Acid as a Ligand for Orphan G Protein-coupled Receptor GPR35

“…Interestingly, elevated plasma levels of kynurenic acid are reported in patients with inflammatory bowel diseases (36,37). The involvement of GPR35 in inflammatory bowel diseases such as ulcerative colitis and Crohn disease and other gastrointestinal disorders should be further investigated.…”

An expanding range of targets for kynurenine metabolites of tryptophan

“…The highest levels of GPR35 are in the intestine where, in patients with inflammatory bowel disease, kynurenic acid levels are significantly greater than in control subjects [43]. The receptor has been implicated in several aspects of gastrointestinal dysfunction including the development of gastric cancer [44].…”