Related Experiment Video
Updated: May 19, 2026

Chronic Salmonella Infection Induced Intestinal Fibrosis
Published on: September 22, 2019
Tryptophan pathway metabotypes associate with disease activity and immune-metabolic dysfunction in inflammatory bowel
Danielle M M Harris1,2,3, Arno R Bourgonje4,5, Peder Rustøen Braadland6,7,8
1Institute of Clinical Molecular Biology, University Medical Center Schleswig-Holstein and Christian-Albrechts-University of Kiel, Kiel, Germany.
Background:
Tryptophan (Trp) metabolism is a central immunometabolic axis in inflammatory bowel disease (IBD) and has been linked to inflammatory activity and immune regulation. While individual Trp metabolites have been associated with disease severity and treatment response, systems-level frameworks to define metabolic subtypes in IBD are lacking.
Objective:
To identify reproducible Trp-related metabolic subtypes ("metabotypes") in IBD and assess their association with disease activity, clinical outcomes, and early disease development.
Design:
We applied unsupervised clustering to serum concentrations of 16 Trp-related metabolites in a discovery cohort of patients with IBD undergoing biologic induction therapy (n=134). Metabotypes were validated in three independent IBD cohorts (total n>2,800), a healthy reference population, and a prospective cohort of first-degree relatives at risk for Crohn's disease. Associations with disease activity, longitudinal outcomes, and metabolic pathways were assessed using multivariable regression and survival analysis.
Results:
Four reproducible metabotypes with distinct metabolite profiles were identified across cohorts: Low Kyna, High Kyna, High Quin, and Balanced. Low Kyna and High Quin metabotypes were consistently associated with increased inflammatory activity and adverse clinical outcomes, including increased risk of treatment escalation and disease progression. Pathway-level analyses revealed alterations in NAD-related, lipid, and amino acid pathways between inflammatory metabotypes. A metabotype resembling inflammatory disease states was enriched in individuals who later developed Crohn's disease in a prospective pre-disease cohort.
Conclusion:
Trp-linked metabotypes define reproducible immunometabolic states in IBD that associate with disease activity and clinical outcomes and may precede disease onset. These findings provide a framework for metabolic stratification and biomarker-guided clinical trials targeting immunometabolic pathways.
Related Concept Videos
Inflammatory Bowel Disease III: Crohn's Disease
Irritable Bowel Syndrome I: Introduction
IBS is a chronic condition that can persist over a long period or recur frequently.
The pathogenesis of IBS involves a complex interplay of the following factors:
Altered...
Inflammatory Bowel Disease III: Diagnostic Studies and Management I-Nutritional Therapy
Diagnostic studies
A colonoscopy is the definitive screening test, distinguishing ulcerative colitis from other colon diseases with similar symptoms. During a colonoscopy test, inflamed mucosa with exudate ulcerations can be observed, and biopsies are taken to determine the histologic characteristics of the colonic...
Inflammatory Bowel Disease II: Ulcerative Colitis
Inflammatory Bowel Disease IV: Pharmacological Management
Pharmacologic...
Inflammatory Bowel Disease I: Introduction
