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Urinary Metabolites Enable Differential Diagnosis and Therapeutic Monitoring of Pediatric Inflammatory Bowel Disease

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Department of Chemistry and Chemical Biology, McMaster University, Hamilton, ON L8S 4M1, Canada
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Department of Pediatrics, Division of Pediatric Gastroenterology and Nutrition, McMaster University, Hamilton, ON L8S 4K1, Canada
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Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON L8S 4K1, Canada
*
Author to whom correspondence should be addressed.
Academic Editor: Thusitha W. Rupasinghe
Metabolites 2021, 11(4), 245; https://doi.org/10.3390/metabo11040245
Received: 5 February 2021 / Revised: 29 March 2021 / Accepted: 10 April 2021 / Published: 15 April 2021
(This article belongs to the Section Metabolomic Profiling Technology)
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. View Full-Text
Keywords: metabolomics; pediatric inflammatory bowel disease; Crohn’s disease; ulcerative colitis; urine; biomarker discovery; diagnosis; exclusive enteral nutrition; treatment monitoring; capillary electrophoresis-mass spectrometry metabolomics; pediatric inflammatory bowel disease; Crohn’s disease; ulcerative colitis; urine; biomarker discovery; diagnosis; exclusive enteral nutrition; treatment monitoring; capillary electrophoresis-mass spectrometry
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MDPI and ACS Style

Yamamoto, M.; Shanmuganathan, M.; Hart, L.; Pai, N.; Britz-McKibbin, P. Urinary Metabolites Enable Differential Diagnosis and Therapeutic Monitoring of Pediatric Inflammatory Bowel Disease. Metabolites 2021, 11, 245. https://doi.org/10.3390/metabo11040245

AMA Style

Yamamoto M, Shanmuganathan M, Hart L, Pai N, Britz-McKibbin P. Urinary Metabolites Enable Differential Diagnosis and Therapeutic Monitoring of Pediatric Inflammatory Bowel Disease. Metabolites. 2021; 11(4):245. https://doi.org/10.3390/metabo11040245

Chicago/Turabian Style

Yamamoto, Mai, Meera Shanmuganathan, Lara Hart, Nikhil Pai, and Philip Britz-McKibbin. 2021. "Urinary Metabolites Enable Differential Diagnosis and Therapeutic Monitoring of Pediatric Inflammatory Bowel Disease" Metabolites 11, no. 4: 245. https://doi.org/10.3390/metabo11040245

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