Characterization of kynurenine pathway in patients with diarrhea-predominant irritable bowel syndrome

Abstract

Our objectives are to demonstrate whether the kynurenine pathway is activated in diarrhea-type irritable bowel syndrome (IBS-D) patients, and whether the neurotoxic metabolite quinolinic acid (QUIN) is out of balance with the neuroprotective metabolite kynurenic acid (KYNA), and further explore whether this can lead to increased expression of N-methyl D-aspartate receptor 2B (NMDAR2B) in the enteric nervous system and in turn leads to intestinal symptoms and mood disorders. All enrolled healthy controls and patients accepted IBS Symptom Severity Scale (IBS-SSS) score, Self-rating Depression Scale (SDS) and Self-rating Anxiety Scale (SAS) anxiety and depression scores, and also underwent colonoscopy to collect ileum and colonic mucosa specimens. The expression of NMDAR2B in intestinal mucosa was detectedby immunofluorescence, and fast-ing serum was collected to detect the tryptophan, kynurenine (KYN), KYNA and QUIN by high performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS). Our results showed that the KYN pathway of IBS-D patients was activated. The production of QUIN and KYNA was imbalanced and resulting in an increased NMDAR2B for patients with IBS-D, which may be involved in intestinal symptoms and mood disorders of IBS-D.