{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T00:49:58Z","timestamp":1792025398503,"version":"4.4.0"},"reference-count":46,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2024,10,15]],"date-time":"2024-10-15T00:00:00Z","timestamp":1728950400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background\/Objectives: Inflammatory bowel diseases primarily encompass Crohn\u2019s disease and ulcerative colitis. Insufficient levels of tryptophan cause an imbalance in the gut microbiota, leading to inflammation in the gastrointestinal tract. The main catabolic pathway of tryptophan is the kynurenine pathway. Our study aims to evaluate serum tryptophan, the kynurenine pathway, and oxidative stress parameters, including total oxidant status and total antioxidant capacity, in patients with Crohn\u2019s disease and ulcerative colitis. Methods: The study included 80 follow-up patients in remission diagnosed with Crohn\u2019s disease and ulcerative colitis who attended the Gastroenterology Outpatient Clinic, as well as 78 healthy controls. Serum tryptophan, kynurenine, 3-hydroxykynurenine, 3-hydroxyanthranilic acid, and kynurenic acid levels were measured with liquid chromatography and tandem mass spectrometry (LC-MS\/MS). All statistical analysis was performed using R version 4.2.1. Statistical Language. Results: Serum tryptophan, 3-hydroxyanthranilic acid, and total antioxidant capacity were lower in patients with ulcerative colitis and Crohn\u2019s disease compared to those in the control group. The serum total oxidant status in the control group was significantly lower than in patients with Crohn\u2019s disease and ulcerative colitis. Conclusions: The results of our research indicate that tryptophan and kynurenine pathway metabolites could potentially contribute to the pathogenesis of inflammatory bowel diseases.<\/jats:p>","DOI":"10.3390\/jcm13206147","type":"journal-article","created":{"date-parts":[[2024,10,16]],"date-time":"2024-10-16T07:58:32Z","timestamp":1729065512000},"page":"6147","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Impaired Kynurenine Pathway in Inflammatory Bowel Disease"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3538-8135","authenticated-orcid":false,"given":"Esra","family":"Payda\u015f Hataysal","sequence":"first","affiliation":[{"name":"Department of Biochemistry, G\u00f6ztepe Prof. Dr. S\u00fcleyman Yal\u00e7\u0131n City Hospital, 34722 Istanbul, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9524-6115","authenticated-orcid":false,"given":"Muslu Kaz\u0131m","family":"K\u00f6rez","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Faculty of Medicine, Selcuk University, 42250 Konya, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4351-1719","authenticated-orcid":false,"given":"Eray Metin","family":"Guler","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Hamidiye Faculty of Medicine, University of Health Sciences, 34480 Istanbul, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1095-6802","authenticated-orcid":false,"given":"Hakan","family":"Vatansev","sequence":"additional","affiliation":[{"name":"Department of Food Processing, Meram Vocational School, Necmettin Erbakan University, 42092 Konya, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2416-0773","authenticated-orcid":false,"given":"Kubra","family":"Bozal\u0131","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Hamidiye Faculty of Medicine, University of Health Sciences, 34480 Istanbul, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Metin","family":"Basaranoglu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Faculty of Medicine, Bezmialem University, 34093 Istanbul, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Husamettin","family":"Vatansev","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine, Selcuk University, 42250 Konya, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1822","DOI":"10.1038\/s41591-019-0675-0","article-title":"Chronic inflammation in the etiology of disease across the life span","volume":"25","author":"Furman","year":"2019","journal-title":"Nat. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3255","DOI":"10.3748\/wjg.v20.i12.3255","article-title":"Dysregulation of mucosal immune response in pathogenesis of inflammatory bowel disease","volume":"20","author":"Xu","year":"2014","journal-title":"World J. Gastroenterol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1038\/nm.4102","article-title":"CARD9 impacts colitis by altering gut microbiota metabolism of tryptophan into aryl hydrocarbon receptor ligands","volume":"22","author":"Lamas","year":"2016","journal-title":"Nat. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1053\/j.gastro.2016.10.012","article-title":"Roles for Intestinal Bacteria, Viruses, and Fungi in Pathogenesis of Inflammatory Bowel Diseases and Therapeutic Approaches","volume":"152","author":"Sartor","year":"2017","journal-title":"Gastroenterology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1093\/ajcn\/63.5.741","article-title":"Epidemiologic analysis of Crohn disease in Japan: Increased dietary intake of n-6 polyunsaturated fatty acids and animal protein relates to the increased incidence of Crohn disease in Japan","volume":"63","author":"Shoda","year":"1996","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Yu, F., Du, Y., Li, C., Zhang, H., Lai, W., Li, S., Ye, Z., Fu, W., Li, S., and Li, X.-G. (2024). Association between metabolites in tryptophan-kynurenine pathway and inflammatory bowel disease: A two-sample Mendelian randomization. Sci. Rep., 14.","DOI":"10.1038\/s41598-023-50990-9"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2769","DOI":"10.1016\/S0140-6736(17)32448-0","article-title":"Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: A systematic review of population-based studies","volume":"390","author":"Ng","year":"2017","journal-title":"Lancet"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e2000461","DOI":"10.1002\/mnfr.202000461","article-title":"An Insight into the Roles of Dietary Tryptophan and Its Metabolites in Intestinal Inflammation and Inflammatory Bowel Disease","volume":"65","author":"Li","year":"2021","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1515\/jomb-2017-0013","article-title":"Is Oxidative Stress Associated with Activation and Pathogenesis of Inflammatory Bowel Disease?","volume":"36","author":"Yuksel","year":"2017","journal-title":"J. Med. Biochem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2371","DOI":"10.3748\/wjg.v11.i16.2371","article-title":"Radical induction theory of ulcerative colitis","volume":"11","author":"Pravda","year":"2005","journal-title":"World J. Gastroenterol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.3109\/10715762.2011.611509","article-title":"Redox biology of the intestine","volume":"45","author":"Circu","year":"2011","journal-title":"Free Radic. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1515\/tjb-2022-0009","article-title":"Relationship between dental caries and saliva\u2019s visfatin levels, total antioxidant capacity (TAC) and total oxidant status (TOS)","volume":"47","author":"Hataysal","year":"2022","journal-title":"Turk. J. Biochem."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Yusufu, I., Ding, K., Smith, K., Wankhade, U.D., Sahay, B., Patterson, G.T., Pacholczyk, R., Adusumilli, S., Hamrick, M.W., and Hill, W.D. (2021). A Tryptophan-Deficient Diet Induces Gut Microbiota Dysbiosis and Increases Systemic Inflammation in Aged Mice. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22095005"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Hou, Y., Li, J., and Ying, S. (2023). Tryptophan Metabolism and Gut Microbiota: A Novel Regulatory Axis Integrating the Microbiome, Immunity, and Cancer. Metabolites, 13.","DOI":"10.3390\/metabo13111166"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1093\/advances\/nmz127","article-title":"Tryptophan Metabolism: A Link Between the Gut Microbiota and Brain","volume":"11","author":"Gao","year":"2020","journal-title":"Adv. Nutr."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Gravina, A.G., Pellegrino, R., Palladino, G., Coppola, A., Brandimarte, G., Tuccillo, C., Ciardiello, F., Romano, M., and Federico, A. (2023). Hericium erinaceus, in combination with natural flavonoid\/alkaloid and B3\/B8 vitamins, can improve inflammatory burden in Inflammatory bowel diseases tissue: An ex vivo study. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1215329"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Wu, L., Hu, Z., Lv, Y., Ge, C., Luo, X., Zhan, S., Huang, W., Shen, X., Yu, D., and Liu, B. (2024). Hericium erinaceus polysaccharides ameliorate nonalcoholic fatty liver disease via gut microbiota and tryptophan metabolism regulation in an aged laying hen model. Int. J. Biol. Macromol., 273.","DOI":"10.1016\/j.ijbiomac.2024.132735"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1186\/s12974-021-02175-2","article-title":"Tryptophan-kynurenine metabolism: A link between the gut and brain for depression in inflammatory bowel disease","volume":"18","author":"Chen","year":"2021","journal-title":"J. Neuroinflamm."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Harris, D.M.M., Szymczak, S., Schuchardt, S., Labrenz, J., Tran, F., Welz, L., Gra\u00dfhoff, H., Zirpel, H., S\u00fcmb\u00fcl, M., and Oumari, M. (2024). Tryptophan degradation as a systems phenomenon in inflammation\u2014An analysis across 13 chronic inflammatory diseases. EBioMedicine, 102.","DOI":"10.1016\/j.ebiom.2024.105056"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1504","DOI":"10.1053\/j.gastro.2017.08.028","article-title":"Increased Tryptophan Metabolism Is Associated with Activity of Inflammatory Bowel Diseases","volume":"153","author":"Nikolaus","year":"2017","journal-title":"Gastroenterology"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1471","DOI":"10.1093\/ibd\/izy103","article-title":"Tryptophan Metabolism through the Kynurenine Pathway is Associated with Endoscopic Inflammation in Ulcerative Colitis","volume":"24","author":"Sofia","year":"2018","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1080\/08830185.2021.1954638","article-title":"Tryptophan metabolites modulate inflammatory bowel disease and colorectal cancer by affecting immune system","volume":"41","author":"Ala","year":"2022","journal-title":"Int. Rev. Immunol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1214","DOI":"10.1002\/ibd.21849","article-title":"Serum analysis of tryptophan catabolism pathway: Correlation with Crohn\u2019s disease activity","volume":"18","author":"Gupta","year":"2012","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1093\/ecco-jcc\/jjx008","article-title":"Third European Evidence-based Consensus on Diagnosis and Management of Ulcerative Colitis. Part 1: Definitions, Diagnosis, Extra-intestinal Manifestations, Pregnancy, Cancer Surveillance, Surgery, and Ileo-anal Pouch Disorders","volume":"11","author":"Magro","year":"2017","journal-title":"J. Crohns Colitis"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1016\/j.clinbiochem.2005.08.008","article-title":"A new automated colorimetric method for measuring total oxidant status","volume":"38","author":"Erel","year":"2005","journal-title":"Clin. Biochem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.clinbiochem.2003.10.014","article-title":"A novel automated method to measure total antioxidant response against potent free radical reactions","volume":"37","author":"Erel","year":"2004","journal-title":"Clin. Biochem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/j.jmsacl.2023.04.003","article-title":"Measurement of kynurenine pathway metabolites by tandem mass spectrometry","volume":"28","author":"Abusoglu","year":"2023","journal-title":"J. Mass. Spectrom. Adv. Clin. Lab."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Verburgt, C.M., Ghiboub, M., Benninga, M.A., de Jonge, W.J., and Van Limbergen, J.E. (2021). Nutritional Therapy Strategies in Pediatric Crohn\u2019s Disease. Nutrients, 13.","DOI":"10.3390\/nu13010212"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1093\/ibd\/izac262","article-title":"Sustained Diet-Induced Remission in Pediatric Crohn\u2019s Disease Is Associated with Kynurenine and Serotonin Pathways","volume":"29","author":"Ghiboub","year":"2023","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1016\/j.jnutbio.2009.01.019","article-title":"l-Tryptophan exhibits therapeutic function in a porcine model of dextran sodium sulfate (DSS)-induced colitis","volume":"21","author":"Kim","year":"2010","journal-title":"J. Nutr. Biochem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1016\/j.immuni.2013.08.003","article-title":"Tryptophan catabolites from microbiota engage aryl hydrocarbon receptor and balance mucosal reactivity via interleukin-22","volume":"39","author":"Zelante","year":"2013","journal-title":"Immunity"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1038\/nature11228","article-title":"ACE2 links amino acid malnutrition to microbial ecology and intestinal inflammation","volume":"487","author":"Hashimoto","year":"2012","journal-title":"Nature"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1111\/j.1365-2133.1977.tb05197.x","article-title":"Pellagra: A still existing disease","volume":"96","author":"Stratigos","year":"1977","journal-title":"Br. J. Dermatol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1007\/BF01648345","article-title":"Rectal manifestations of pellagra","volume":"1","author":"Segal","year":"1986","journal-title":"Int. J. Color. Dis."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1177\/039463200802100205","article-title":"Inflamed intestinal mucosa features a specific epithelial expression pattern of indoleamine 2,3-dioxygenase","volume":"21","author":"Ferdinande","year":"2008","journal-title":"Int. J. Immunopathol. Pharmacol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1097\/MEG.0b013e328351c1c2","article-title":"Indoleamine 2,3-dioxygenase expression in human inflammatory bowel disease","volume":"24","author":"Zhou","year":"2012","journal-title":"Eur. J. Gastroenterol. Hepatol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1756284819881304","DOI":"10.1177\/1756284819881304","article-title":"Increased expression of kynurenine aminotransferases mRNA in lymphocytes of patients with inflammatory bowel disease","volume":"12","author":"Szymona","year":"2019","journal-title":"Therap Adv. Gastroenterol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1136\/gut.42.4.485","article-title":"Impairment of intestinal glutathione synthesis in patients with inflammatory bowel disease","volume":"42","author":"Sido","year":"1998","journal-title":"Gut"},{"key":"ref_39","first-page":"362","article-title":"Markers of lipid peroxidation and antioxidant status in the serum and saliva of patients with active Crohn disease","volume":"128","author":"Szczeklik","year":"2018","journal-title":"Pol. Arch. Intern. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3829","DOI":"10.1039\/C6NJ03980D","article-title":"Dual antioxidant\/pro-oxidant behavior of the tryptophan metabolite 3-hydroxyanthranilic acid: A theoretical investigation of reaction mechanisms and kinetics","volume":"41","author":"Galano","year":"2017","journal-title":"New J. Chem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1515\/pteridines.2002.13.4.140","article-title":"Tryptophan Metabolites as Scavengers of Reactive Oxygen and Chlorine Species","volume":"13","author":"Weiss","year":"2002","journal-title":"Pteridines"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1054797","DOI":"10.1155\/2018\/1054797","article-title":"The Tryptophan Pathway Targeting Antioxidant Capacity in the Placenta","volume":"2018","author":"Xu","year":"2018","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Bantounou, M., Plascevic, J., and Galley, H.F. (2022). Melatonin and Related Compounds: Antioxidant and Anti-Inflammatory Actions. Antioxidants, 11.","DOI":"10.3390\/antiox11030532"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Hassanzad, M., and Hajian-Tilaki, K. (2024). Methods of determining optimal cut-point of diagnostic biomarkers with application of clinical data in ROC analysis: An update review. BMC Med. Res. Methodol., 24.","DOI":"10.1186\/s12874-024-02198-2"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1002\/1097-0142(1950)3:1<32::AID-CNCR2820030106>3.0.CO;2-3","article-title":"Index for rating diagnostic tests","volume":"3","author":"Youden","year":"1950","journal-title":"Cancer"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"3762651","DOI":"10.1155\/2017\/3762651","article-title":"Defining an Optimal Cut-Point Value in ROC Analysis: An Alternative Approach","volume":"2017","author":"Unal","year":"2017","journal-title":"Comput. Math. Methods Med."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/13\/20\/6147\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:13:55Z","timestamp":1760112835000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/13\/20\/6147"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,15]]},"references-count":46,"journal-issue":{"issue":"20","published-online":{"date-parts":[[2024,10]]}},"alternative-id":["jcm13206147"],"URL":"https:\/\/doi.org\/10.3390\/jcm13206147","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,15]]}}}