Urinary Metabolites Enable Differential Diagnosis and Therapeutic Monitoring of Pediatric Inflammatory Bowel Disease
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 I...
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MDPI AG
2021-04-01
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| Series: | Metabolites |
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| Online Access: | https://www.mdpi.com/2218-1989/11/4/245 |
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| author | Mai Yamamoto Meera Shanmuganathan Lara Hart Nikhil Pai Philip Britz-McKibbin |
| author_facet | Mai Yamamoto Meera Shanmuganathan Lara Hart Nikhil Pai Philip Britz-McKibbin |
| author_sort | Mai Yamamoto |
| collection | DOAJ |
| description | 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 (<i>n</i> = 18) and UC (<i>n</i> = 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 (<i>p</i> < 0.05). Excellent discrimination of CD from UC was achieved based on the urinary serine:indoxylsulfate ratio (<i>AUC</i> = 0.972; <i>p</i> = 3.21 × 10<sup>−5</sup>). 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. |
| first_indexed | 2024-03-10T12:17:39Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2218-1989 |
| language | English |
| last_indexed | 2024-03-10T12:17:39Z |
| publishDate | 2021-04-01 |
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| series | Metabolites |
| spelling | doaj.art-bc2776e92cde4554be909dc7f28ddbf12023-11-21T15:45:59ZengMDPI AGMetabolites2218-19892021-04-0111424510.3390/metabo11040245Urinary Metabolites Enable Differential Diagnosis and Therapeutic Monitoring of Pediatric Inflammatory Bowel DiseaseMai Yamamoto0Meera Shanmuganathan1Lara Hart2Nikhil Pai3Philip Britz-McKibbin4Department of Chemistry and Chemical Biology, McMaster University, Hamilton, ON L8S 4M1, CanadaDepartment of Chemistry and Chemical Biology, McMaster University, Hamilton, ON L8S 4M1, CanadaDepartment of Pediatrics, Division of Pediatric Gastroenterology and Nutrition, McMaster University, Hamilton, ON L8S 4K1, CanadaDepartment of Pediatrics, Division of Pediatric Gastroenterology and Nutrition, McMaster University, Hamilton, ON L8S 4K1, CanadaDepartment of Chemistry and Chemical Biology, McMaster University, Hamilton, ON L8S 4M1, CanadaRates 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 (<i>n</i> = 18) and UC (<i>n</i> = 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 (<i>p</i> < 0.05). Excellent discrimination of CD from UC was achieved based on the urinary serine:indoxylsulfate ratio (<i>AUC</i> = 0.972; <i>p</i> = 3.21 × 10<sup>−5</sup>). 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.https://www.mdpi.com/2218-1989/11/4/245metabolomicspediatric inflammatory bowel diseaseCrohn’s diseaseulcerative colitisurinebiomarker discovery |
| spellingShingle | Mai Yamamoto Meera Shanmuganathan Lara Hart Nikhil Pai Philip Britz-McKibbin Urinary Metabolites Enable Differential Diagnosis and Therapeutic Monitoring of Pediatric Inflammatory Bowel Disease Metabolites metabolomics pediatric inflammatory bowel disease Crohn’s disease ulcerative colitis urine biomarker discovery |
| title | Urinary Metabolites Enable Differential Diagnosis and Therapeutic Monitoring of Pediatric Inflammatory Bowel Disease |
| title_full | Urinary Metabolites Enable Differential Diagnosis and Therapeutic Monitoring of Pediatric Inflammatory Bowel Disease |
| title_fullStr | Urinary Metabolites Enable Differential Diagnosis and Therapeutic Monitoring of Pediatric Inflammatory Bowel Disease |
| title_full_unstemmed | Urinary Metabolites Enable Differential Diagnosis and Therapeutic Monitoring of Pediatric Inflammatory Bowel Disease |
| title_short | Urinary Metabolites Enable Differential Diagnosis and Therapeutic Monitoring of Pediatric Inflammatory Bowel Disease |
| title_sort | urinary metabolites enable differential diagnosis and therapeutic monitoring of pediatric inflammatory bowel disease |
| topic | metabolomics pediatric inflammatory bowel disease Crohn’s disease ulcerative colitis urine biomarker discovery |
| url | https://www.mdpi.com/2218-1989/11/4/245 |
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