Evaluating the role of kynurenine/tryptophan ratio as an indicator of disease activity in Indian patients with inflammatory bowel disease. A case-control study.

Background: Tryptophan (T), an essential amino acid, is primarily metabolized (∼90%) to kynurenine (K) by indoleamine 2,3-dioxygenase 1 (IDO1) mainly in intestinal cells. In inflammatory bowel disease (IBD), there is an increase in IDO1 activity which would increase Kynurenine levels and Kynurenine/Tryptophan (K/T) ratio. We hypothesize that alteration in K/T may be an indicator of disease severity in IBD.

Methods: 55 healthy controls (HC), 55 Ulcerative colitis (UC) (35 active and 20 remission) and 30 Crohn's disease (CD) (20 active and 10 remission) were enrolled from November 2020 to March 2023. Plasma Kyn & Trp were simultaneously estimated using ultra-high-pressure liquid chromatography (UPLC). K/T ratio was correlated with disease activity and fecal calprotectin. In 25 patients follow-up samples were also collected with change in disease activity.

Results: Median K/T ratio was significantly higher in patients with active disease as compared to those in remission and HC (p < .0001). A cut-off of ≤41 distinguished remission/healthy controls with a sensitivity of 92.73%, specificity of 76.36%, and an AUC of 0.9 (95% CI: 0.83-0.95, p < .001). The K/T ratio correlated with FC levels at a diagnostic cut-off of 250 µg/g. A significant reduction in K/T ratio with disease activity was noted in 80% of follow-up patients.

Conclusion: The K/T ratio with a cut-off of 41, correlated with the disease activity in 82% of patients, suggesting that the K/T ratio alters remarkably with disease activity in IBD patients. These findings can be further assessed for disease marker in a larger cohort of IBD patients.