Serum Tryptophan And Profiling Of Tryptophan Metabolism In Human Ulcerative Colitis

Ulcerative colitis (UC) is a chronic inflammatory disease of therectum and colon. There is longstanding evidence demonstrating that UCresults from an excessive and poorly controlled mucosal immune responseto commensal flora in genetically susceptible hosts. However, the precisecause of UC is still unknown. The diagnostic markers’ specificity andsensitivity are not strong. So, it is lack of gold standard. The currenttreatment targets for disease are Inducing and maintaining clinicalremission and mucosal healing. But there is no satisfactory treatment. So,the pathogenesis, diagnosis and therapy in UC become a hotspot. Recentstudies suggest that amino acids metabolic routes play an important role inintestinal tract inflammatory disease. L-Tryptophan (Trp) is an essentialamino acid whose metabolism has been linked with autoimmunity. Andalterations of Trp metabolism may give rise to gastrointestinal dysfunction,such as inflammatory bowel disease (IBD), irritable bowel syndrome (IBS),celiac disease and diverticulitis. Therefore, studying serum tryptophan andits metabolites in patients with UC may resolve these issues to open a newway of thinking.Serum samples were acquired from40individuals:20UC patients(active period and inactive period) serum and20HVs serum. The diagnosisfor each patient was based on clinical symptoms, endoscopic, radiographic,and histological examinations. The Montreal Classification was used fordisease phenotype. Disease activity was assessed by the modified MayoIndex. Tryptophan and its key metabolites in serum and urine weremeasured by liquid chromatography mass spectrometry (LC-MS/MS). Comparisons between active UC cohorts，inactive UC cohorts and HVswere made by one-way analysis of variance. Comparisons between UCcohorts and HVs were made by t tests. The association of two substanceswas made using linear regression analysis.Results of Serum Trp detection and analysis show that1.Comparedpatients with active UC, the level of tryptophan in patients with inactiveUC and HVs was significantly lower (P<0.05). While, there was notsignificant difference between patients with inactive UC and HVs.2.Serum tryptophan in active UC patients was inversely related to ESR (r=-0.520*, P=0.024); Serum tryptophan in active UC patients was inverselyrelated to CRP (r=-0.523*, P=0.016).3. After conventional treatment, thelevel of serum tryptophan was significantly elevated (P<0.05).Results of Serum Trp metabolism detection and analysis show that inserum of UC patients (active period), xanthurenic acid (XA),3-hydroxyanthranilic acid (HAA), serotonin, indole-3-lactic acid (ILA),indole-3-propionic acid (IPA) were the metabolites prominently decrease,whereas, anthranilic acid (AA),5-hydroxy-indole-3-acetic acid (HIAA)were the metabolites prominently increase. In all of difference, XA was themetabolite most prominently changes.In this study, we detected serum Trp in Patients with UC (active periodand inactive period) and HVs and investigated the possible role of thedevelopment and clinical significance of serum Trp levels in UC. At thesame time, we detected serum the key Trp metabolites within thekynurenine, serotonin, as well as the bacterial degradation pathways byLC-MS/MS in Patients with active UC and HVs. As we know, it is themost comprehensive tryptophan metabolism analysis using on UC.Through the comprehensive analysis and comparison of serum Trpmetabolism, we found the differences Trp metabolites in differentmetabolic pathways between UC patients and HVs. In all of difference, XA was the metabolite most prominently changes, which settles goodfoundation for further study, as well as understand the overall situation ofTrp metabolic profiles in UC patients, and the role of key metabolites in thepathogenesis of ulcerative colitis. It may provide a reference for a betterunderstanding of the pathogenesis of UC to find specific diagnosticmarkers and new therapeutic approaches.