Fecal Amino Acid Analysis in Newly Diagnosed Pediatric Inflammatory Bowel Disease: A Multicenter Case-Control Study

Abstract

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.

Bovine milk-derived extracellular vesicles prevent gut inflammation by regulating lipid and amino acid metabolism

“…Valine belongs to branched chain amino acids, and the increased level in fecal samples was demonstrated to have positive association with the severity of IBD. 15 Arginine was decreased in IBD patients, 14 while mEVs increased its concentration in our results. Arginine, a semi-essential amino acid, is the precursor of nitric oxide (NO) and polyamines, which played a vital role in B-cell maturation, T-cell proliferation, and cytokine production.…”

“…13 Previous studies reported that about 17 fecal amino acids were higher in IBD patients compared with healthy individuals. 14,15 In brief, the regulation of lipid and amino acid metabolism is believed to be a promising method to treat IBD.…”

A Clinical Trial of the Effects of a Dietary Pattern on Health Metrics and Fecal Metabolites in Volunteers With Risk of Cardiovascular Disease

“…Significantly higher levels of threonine were found in the fecal metabolites of patients with irritable bowel syndrome (IBD) and ankylosing spondylitis (AS) ( 27 , 48 ). Meanwhile, increased levels of lysine, alanine, and glycine have also been shown to correlate with malabsorption due to intestinal inflammation ( 49 , 50 ). Therefore, the decreased fecal levels of alanine, threonine, aspartate, lysine and glycine could reflect the improved inflammatory status in vivo .…”

Inflammatory Bowel Disease and COVID-19: How Microbiomics and Metabolomics Depict Two Sides of the Same Coin

“…Moreover, in the group of children with UC, serum histidine inversely correlated with erythrocyte sedimentation rate (ESR). Histidine fecal levels have been positively associated with more extended disease in UC but not in CD pediatric patients ( Jagt et al, 2021 ). A possible explanation may be either the colonic leakage of histidine and other amino acids or malabsorption.…”