Untargeted, High‐Resolution Metabolomics in Pediatric Eosinophilic Esophagitis

Background/Objectives: Eosinophilic esophagitis (EoE) is an inflammatory disease of unclear etiology. The aim of this study was to use untargeted plasma metabolomics to identify metabolic pathway alterations associated with EoE to better understand the pathophysiology. Methods: This prospective, case‐control study included 72 children, aged 1–17 years, undergoing clinically indicated upper endoscopy (14 diagnosed with EoE and 58 controls). Fasting plasma samples were analyzed for metabolomics by high‐resolution dual‐chromatography mass spectrometry. Analysis was performed on sex‐matched groups at a 2:1 ratio. Significant differences among the plasma metabolite features between children with and without EoE were determined using multivariate regression analysis and were annotated with a network‐based algorithm. Subsequent pathway enrichment analysis was performed. Results: Patients with EoE had a higher proportion of atopic disease (85.7% vs 50%, P = 0.019) and any allergies (100% vs 57.1%, P = 0.0005). Analysis of the dual chromatography features resulted in a total of 918 metabolites that differentiated EoE and controls. Glycerophospholipid metabolism was significantly enriched with the greatest number of differentiating metabolites and overall pathway enrichment ( P < 0.01). Multiple amino and fatty acid pathways including linoleic acid were also enriched, as well as pyridoxine metabolism ( P < 0.01). Conclusions: In this pilot study, we found differences in metabolites involved in glycerophospholipid and inflammation pathways in pediatric patients with EoE using untargeted metabolomics, as well as overlap with amino acid metabolome alterations found in atopic disease.