M Anthony Sofia1, Matthew A Ciorba2, Katherine Meckel1, Chai K Lim3, Gilles J Guillemin3, Christopher R Weber4, Marc Bissonnette1, Joel R Pekow1. 1. Department of Medicine, Section of Gastroenterology, Hepatology, and Nutrition, University of Chicago Medicine, Chicago, IL, United States. 2. Division of Gastroenterology, Washington University in St. Louis, St. Louis, MO, United States. 3. Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW, Australia. 4. Department of Pathology, University of Chicago Medicine, Chicago, IL, United States.
Abstract
Background and Aims: Mucosal appearance on endoscopy is an important indicator of inflammatory burden and determines prognosis in ulcerative colitis (UC). Inflammation induces tryptophan metabolism along the kynurenine pathway (KP) and yields immunologically relevant metabolites. We sought to examine whether changes in serum tryptophan metabolites and tissue expression of KP enzymes are associated with UC endoscopic and histologic disease severity. Methods: Serum and mucosal samples were prospectively obtained at colonoscopy in patients with UC. Mayo disease activity scores, demographics, smoking status, medications, and outcomes were collected. Serum tryptophan metabolites were analyzed using ultra-high performance liquid chromatography (uHPLC), and gas chromatography-mass spectrometry (GC-MS), and enzyme expression was determined by quantitative real-time polymerase chain reaction. Metabolite and enzyme levels were compared by endoscopic subscore, clinical disease activity, time to surgery, and hospitalization. Results: This study included 99 patients with Mayo endoscopic subscores 0-3. Kynurenic acid/tryptophan ratio (KYNA/T) and expression of indolamine 2,3-dioxygenase 1 (IDO1), tryptophan 2,3-dioxygenase, kynurinase, and kynurenine monooxygenase correlated positively with endoscopic subscore. Adjusting for age of diagnosis, smoking status, disease extent, and medications yielded significant odds of endoscopic inflammation with increasing KYNA/T (OR 1.0015, P = 0.0186) and IDO1 expression (OR 1.0635, P = 0.0215). The highest tertile ratio of KYNA/T had shorter time to surgery (P = 0.009) and hospitalization (P = 0.01) than the lowest. Conclusions: Increasing KYNA/T is closely associated with endoscopic inflammation and predictive of disease outcomes in patients with UC. These findings identify this novel metabolic association and further support the role of the KP in regulating mucosal inflammation in UC. 10.1093/ibd/izy103_video1izy103.video15788135676001.
Background and Aims: Mucosal appearance on endoscopy is an important indicator of inflammatory burden and determines prognosis in ulcerative colitis (UC). Inflammation induces tryptophan metabolism along the kynurenine pathway (KP) and yields immunologically relevant metabolites. We sought to examine whether changes in serum tryptophan metabolites and tissue expression of KP enzymes are associated with UC endoscopic and histologic disease severity. Methods: Serum and mucosal samples were prospectively obtained at colonoscopy in patients with UC. Mayo disease activity scores, demographics, smoking status, medications, and outcomes were collected. Serum tryptophan metabolites were analyzed using ultra-high performance liquid chromatography (uHPLC), and gas chromatography-mass spectrometry (GC-MS), and enzyme expression was determined by quantitative real-time polymerase chain reaction. Metabolite and enzyme levels were compared by endoscopic subscore, clinical disease activity, time to surgery, and hospitalization. Results: This study included 99 patients with Mayo endoscopic subscores 0-3. Kynurenic acid/tryptophan ratio (KYNA/T) and expression of indolamine 2,3-dioxygenase 1 (IDO1), tryptophan 2,3-dioxygenase, kynurinase, and kynurenine monooxygenase correlated positively with endoscopic subscore. Adjusting for age of diagnosis, smoking status, disease extent, and medications yielded significant odds of endoscopic inflammation with increasing KYNA/T (OR 1.0015, P = 0.0186) and IDO1 expression (OR 1.0635, P = 0.0215). The highest tertile ratio of KYNA/T had shorter time to surgery (P = 0.009) and hospitalization (P = 0.01) than the lowest. Conclusions: Increasing KYNA/T is closely associated with endoscopic inflammation and predictive of disease outcomes in patients with UC. These findings identify this novel metabolic association and further support the role of the KP in regulating mucosal inflammation in UC. 10.1093/ibd/izy103_video1izy103.video15788135676001.
Authors: P Persoons; S Vermeire; K Demyttenaere; B Fischler; J Vandenberghe; L Van Oudenhove; M Pierik; T Hlavaty; G Van Assche; M Noman; P Rutgeerts Journal: Aliment Pharmacol Ther Date: 2005-07-15 Impact factor: 8.171
Authors: Susanna Nikolaus; Berenice Schulte; Natalie Al-Massad; Florian Thieme; Dominik M Schulte; Johannes Bethge; Ateequr Rehman; Florian Tran; Konrad Aden; Robert Häsler; Natalie Moll; Gregor Schütze; Markus J Schwarz; Georg H Waetzig; Philip Rosenstiel; Michael Krawczak; Silke Szymczak; Stefan Schreiber Journal: Gastroenterology Date: 2017-08-19 Impact factor: 22.682
Authors: L Ferdinande; P Demetter; C Perez-Novo; A Waeytens; J Taildeman; I Rottiers; P Rottiers; M De Vos; C A Cuvelier Journal: Int J Immunopathol Pharmacol Date: 2008 Apr-Jun Impact factor: 3.219
Authors: Piotr Paluszkiewicz; Wojciech Zgrajka; Tomasz Saran; Janusz Schabowski; Jose L Valverde Piedra; Olexandr Fedkiv; Sofia Rengman; Stefan G Pierzynowski; Waldemar A Turski Journal: Amino Acids Date: 2008-10-05 Impact factor: 3.520
Authors: Giovanni Barbara; Vincenzo Stanghellini; Roberto De Giorgio; Cesare Cremon; Graeme S Cottrell; Donatella Santini; Gianandrea Pasquinelli; Antonio M Morselli-Labate; Eileen F Grady; Nigel W Bunnett; Stephen M Collins; Roberto Corinaldesi Journal: Gastroenterology Date: 2004-03 Impact factor: 22.682
Authors: David M Alvarado; Baosheng Chen; Micah Iticovici; Ameet I Thaker; Nattalie Dai; Kelli L VanDussen; Nurmohammad Shaikh; Chai K Lim; Gilles J Guillemin; Phillip I Tarr; Matthew A Ciorba Journal: Gastroenterology Date: 2019-07-17 Impact factor: 22.682
Authors: Christopher S Smillie; Moshe Biton; Jose Ordovas-Montanes; Keri M Sullivan; Grace Burgin; Daniel B Graham; Rebecca H Herbst; Noga Rogel; Michal Slyper; Julia Waldman; Malika Sud; Elizabeth Andrews; Gabriella Velonias; Adam L Haber; Karthik Jagadeesh; Sanja Vickovic; Junmei Yao; Christine Stevens; Danielle Dionne; Lan T Nguyen; Alexandra-Chloé Villani; Matan Hofree; Elizabeth A Creasey; Hailiang Huang; Orit Rozenblatt-Rosen; John J Garber; Hamed Khalili; A Nicole Desch; Mark J Daly; Ashwin N Ananthakrishnan; Alex K Shalek; Ramnik J Xavier; Aviv Regev Journal: Cell Date: 2019-07-25 Impact factor: 41.582
Authors: Baosheng Chen; David M Alvarado; Micah Iticovici; Nathan S Kau; Haeseong Park; Parag J Parikh; Dinesh Thotala; Matthew A Ciorba Journal: Cancer Immunol Res Date: 2020-03-03 Impact factor: 11.151
Authors: Jiayu Ye; Lauren A E Erland; Sandeep K Gill; Stephanie L Bishop; Andrea Verdugo-Meza; Susan J Murch; Deanna L Gibson Journal: Biomolecules Date: 2021-05-15