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 increase of N-methyl D-aspartate receptor 2B (NMDAR2B) expression 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 detected by immunofluorescence, and fasting serum was collected to detect the tryptophan (Trp), kynurenine (KYN), KYNA and QUIN by high performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS). Our results showed that the kynurenine 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.

Molecular Mechanisms of Microbiota-Mediated Pathology in Irritable Bowel Syndrome

“…On the other hand, both kynurenic and quinolinic acid can bind the NMDA receptor located on neuronal networks in the spinal cord, which is involved in peripheral sensitization and visceral hyperalgesia [ 89 ]. Indeed, quinolinic and kynurenic acid production is activated with increased expression of the NMDA receptor 2B in IBS-D patients [ 215 ]. Additional examinations regarding this pathway in IBS are needed.…”

A Review of the Health Benefits of Food Enriched with Kynurenic Acid

“…The presence of KYNA in human blood serum has been repeatedly reported ( Table S1 ). The content of KYNA in the serum obtained from adult healthy humans ranges from 0.016 to 0.071 μM and is within the same limits in the serum obtained from children [ 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 ].…”

Tryptophan‐derived serotonin‐kynurenine balance in immune activation and intestinal inflammation

“…11,195,197 In fact, many small-molecule IDO1 inhibitors are being investigated in combination with immunotherapy, chemotherapy or radiotherapy in phase II and III clinical trials for different types of cancers. 201 Alterations in the IDO expression, kynurenine/tryptophan ratios and ratios of downstream metabolites including quinolinic acid and KYNA have also been associated with IBS-D patients, 202 diverticulitis, 126 and celiac disease. 203…”

“…Alterations in the IDO expression, kynurenine/tryptophan ratios and ratios of downstream metabolites including quinolinic acid and KYNA have also been associated with IBS‐D patients, 202 diverticulitis, 126 and celiac disease. 203 …”