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Fecal Amino Acid Analysis in Newly Diagnosed Pediatric Inflammatory Bowel Disease: A Multicenter Case-Control Study
Jasmijn Z Jagt1, Eduard A Struys2, Ibrahim Ayada1
1Department of Pediatric Gastroenterology, Emma Children's Hospital, Amsterdam UMC, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands.
Insights
Fecal amino acid profiles can help differentiate pediatric inflammatory bowel disease (IBD) from controls. Specific amino acids like tryptophan and valine may serve as future biomarkers for diagnosing IBD in children.
Area of Science:
- Gastroenterology
- Metabolomics
- Pediatric Medicine
Background:
- Fecal metabolomic profiles offer insights into pediatric inflammatory bowel disease (IBD) pathophysiology.
- The specific role of amino acids in pediatric IBD requires further elucidation.
Purpose of the Study:
- To assess fecal amino acid profiles in pediatric IBD patients.
- To explore the potential of fecal amino acids as biomarkers for IBD diagnosis and personalized medicine.
Main Methods:
- A case-control study included treatment-naïve pediatric IBD patients and age/sex-matched controls.
- Fecal amino acid profiles were analyzed using targeted high-performance liquid chromatography.
- A random forest classifier was employed to build a predictive model for IBD detection.
Main Results:
- IBD patients were distinguished from controls with 82% accuracy, with 29 unique amino acids identified as key differentiating factors.
- Increased levels of tryptophan, taurine, alanine, ornithine, valine, histidine, and leucine were prominent in IBD patients.
- While IBD phenotype could not be predicted, elevated tryptophan, valine, and histidine correlated with extended disease in ulcerative colitis.
Conclusions:
- Fecal amino acids show promise in understanding host-microbial interactions in IBD.
- These findings suggest fecal amino acids could become valuable biomarkers for pediatric IBD diagnosis and personalized treatment strategies.
Background:
Fecal metabolomic profiles differ between pediatric inflammatory bowel disease (IBD) patients and controls and may provide new insights in the pathophysiology of IBD. The role of amino acids, however, is not fully elucidated. We aimed to assess fecal amino acid profiles in pediatric IBD.
Methods:
In this case-control study, treatment-naïve, newly diagnosed pediatric IBD patients and a non-IBD control group, matched based on sex and age, were included in 2 tertiary centres. Fecal amino acid profiles were assessed using a targeted high-performance liquid chromatography technique. A random forest classifier method was used to develop a prediction model differentiating IBD from controls and predicting IBD phenotype. The association between IBD localization and amino acid concentrations was tested with ordinal regression models.
Results:
We included 78 newly diagnosed IBD patients (40 Crohn's disease [CD], 38 ulcerative colitis [UC]) and 105 controls. Patients with IBD could be differentiated from controls with an accuracy of 82% (sensitivity 63%, specificity 97%). Twenty-nine out of the 42 measured unique amino acids were included in the prediction model. Increased levels of tryptophan, taurine, alanine, ornithine, valine, histidine, and leucine were the most differentiating features. Children with CD and UC could be differentiated from the controls with an accuracy of 80% and 90%, respectively. Inflammatory bowel disease phenotype could not be predicted. Tryptophan, valine, and histidine levels were positively associated with more extended disease in UC patients (P < .05).
Conclusions:
Fecal amino acids may enhance understanding of the role of host-microbial interactions in the pathophysiology of IBD and may evolve into biomarkers for pediatric IBD diagnostic and personalized medicine.
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