Abstract
Rates of pediatric Crohn’s disease (CD) and ulcerative colitis (UC) are increasing globally. Differentiation of these inflammatory bowel disease (IBD) subtypes however can be challenging when relying on invasive endoscopic approaches. We sought to identify urinary metabolic signatures of pediatric IBD at diagnosis, and during induction treatment. Nontargeted metabolite profiling of urine samples from CD (n = 18) and UC (n = 8) in a pediatric retrospective cohort study was performed using multisegment injection-capillary electrophoresis-mass spectrometry. Over 122 urinary metabolites were reliably measured from pediatric IBD patients, and unknown metabolites were identified by tandem mass spectrometry. Dynamic changes in sum-normalized urinary metabolites were also monitored following exclusive enteral nutrition (EEN) or corticosteroid therapy (CS) in repeat urine samples collected over 8 weeks. Higher urinary excretion of indoxyl sulfate, hydroxyindoxyl sulfate, phenylacetylglutamine, and sialic acid were measured in CD as compared to UC patients, but lower threonine, serine, kynurenine, and hypoxanthine (p < 0.05). Excellent discrimination of CD from UC was achieved based on the urinary serine:indoxylsulfate ratio (AUC = 0.972; p = 3.21 × 10−5). Urinary octanoyl glucuronide, pantothenic acid, and pyridoxic acid were also identified as specific dietary biomarkers of EEN in pediatric IBD patients who achieved clinical remission. This work may complement or replace existing strategies in the diagnosis and early management of children with IBD.
Highlights
Crohn’s disease (CD) and ulcerative colitis (UC) carry a significant global disease burden [1]
inflammatory bowel disease (IBD) diagnosis and CD/UC classification was determined by combined endoscopic findings, histopathology and magnetic resonance enterography findings
57% of IBD patients achieved full clinical remission, and 32% showed a clinical response with significantly lower inflammation after 8 weeks of enteral nutrition (EEN) or corticosteroid therapy (CS) therapy as compared to baseline
Summary
Crohn’s disease (CD) and ulcerative colitis (UC) carry a significant global disease burden [1]. Higher severity disease coincides with a greater utilization of healthcare resources due to accrued complications of surgical involvement, poor nutrition, and medication side effects [4]. Exclusive enteral nutrition (EEN) is first-line treatment for induction of remission in children with CD as it has not been proven effective in pediatric UC [7]. Neither modality leads to conclusive results in all cases, with pediatric patients prone to higher rates of indeterminate colitis, or IBD-unclassified [9]. These diagnostic dilemmas reflect the poorly understood etiology of IBD in children, early onset IBD, which is mediated by a complex interplay of genetic, immunological and environmental factors
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