The role of urine metabolomics in the diagnosis and management of adult and pediatric Crohn's disease and ulcerative colitis

Abstract

Introduction: Urine metabolomics offers a non-invasive approach to diagnose and manage inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), by identifying distinct metabolic signatures.

Objectives: This narrative review summarizes current findings on urinary metabolites in IBD, evaluating their roles in disease differentiation, assessment of activity, and monitoring therapeutic response.

Methods: A comprehensive literature search of PubMed and MEDLINE up to October 2023 was conducted using keywords, such as 'urine metabolomics', 'inflammatory bowel disease', 'Crohn's disease', 'ulcerative colitis', and 'urinary biomarkers'. Studies were included that described alterations to metabolic pathways, including those related to the urea cycle, central energy metabolism (Krebs cycle), amino acid metabolism, and neurotransmitters.

Results: Specific urinary metabolites differentiate IBD patients from healthy controls and between CD and UC. Decreased urinary levels of hippurate, acetate, methanol, formate, and methylamine are observed in IBD, indicating altered gut microbiota. In CD patients, urea cycle alterations include reduced urinary urea and ornithine with increased arginine. Changes in Krebs cycle intermediates show decreased citrate and succinate in adults, but increased fumarate and isocitrate in pediatric patients, reflecting energy metabolism differences. Amino acid metabolism differs by age: Adults exhibit decreased urinary asparagine, lysine, and histidine, while pediatric patients show increased methionine, proline, aspartic acid, and isoleucine. Elevated urinary neurotransmitters like dopamine are noted in pediatric IBD patients. Urine metabolomics also can monitor treatment efficacy by distinguishing responders from non-responders to therapies and differentiating active disease from remission.

Conclusion: Urine metabolomics provides promising, non-invasive biomarkers to enhance IBD diagnostics by distinguishing CD from UC and offering insights into underlying metabolic disturbances, paving the way for more precise, accessible patient care.

Keywords: Crohn’s disease; Inflammatory bowel disease; children; diagnostics; metabolomics; microbiome; pediatrics; ulcerative colitis; urine metabolites.