Tryptophan metabolites as biomarkers to predict the severity and prognosis of acute ischemic stroke patients
Background: A growing body of evidence indicates alterations in metabolite levels and enzyme activities associated with the conversion of tryptophan (TRP) throughout the course of cerebral ischemia. In this study we aim to explore the potential relationship between TRP metabolism and clinical prognosis in acute ischemic stroke (AIS) patients of mainland China. Methods: Blood samples were obtained from a cohort of 304 AIS patients. The concentrations of ten TRP metabolites were quantified utilizing liquid chromatography-tandem mass spectrometry. LASSO regression and random forest algorithms were employed to identify key TRP metabolism parameters associated with prognosis. Results: The metabolites TRP, 5-hydroxytryptamine (5-HTP), 3-hydroxyanthranilic acid (3-HAA)/3-hydroxykynurenine (3-HKYN) showed a negative correlation with the NIHSS score, while 3-HKYN, kynurenic acid (KYNA), 3-HKYN/kynurenine (KYN), KYN/TRP, KYNA/KYN, 3-HKYN/TRP, N-formylkynurenine (NFK)/TRP and KYNA/TRP ratio exhibited a positive correlation with the NIHSS score. Three robust parameters related to TRP metabolism were identified. Multivariable logistic regression analysis, adjusted for covariates, revealed that TRP (odds ratio [OR] = 0.46, 95% confidence interval [CI]: 0.26 - 0.76, p = 0.004), the KYN/TRP ratio (OR = 2.06, 95% CI: 1.23 - 3.60, p = 0.008), and the KYNA/TRP ratio (OR = 2.15, 95% CI: 1.23 - 4.12, p = 0.014) were independently associated with poor functional prognosis. Conclusions: The results of this study indicate that TRP metabolism is associated with the severity and prognosis of AIS. The TRP, KYN/TRP ratio and KYNA/TRP ratio may serve as potential biomarkers for 3-month prognostic evaluation.