Metabolomic comparison of postprandial distress syndrome patients with and without duodenal eosinophilia

Author:

Dalal Stuti1,Ajit Deepa2,Friesen Chance S.3,Shakhnovich Valentina4,Singh Meenal3,Colombo Jennifer M.3,Schurman Jennifer V.3,Friesen Craig A.3ORCID

Affiliation:

1. University of Missouri Kansas City School of Medicine Kansas City Missouri USA

2. Metabolon, Inc. Durham North Carolina USA

3. Division of Gastroenterology, Hepatology, and Nutrition Children's Mercy Kansas City Kansas City Missouri USA

4. Ironwood Pharmaceuticals Boston Massachusetts USA

Abstract

AbstractObjectiveIn functional dyspepsia patients, duodenal mucosal eosinophilia has been associated with early satiety but is not present in all patients suggesting varied pathways to symptom generation. The objective of the current study was to explore metabolic differences comparing those with duodenal mucosal eosinophilia to those without eosinophilia.MethodsThis study was conducted utilizing an existing biorepository. Patients had plasma samples obtained at the time of endoscopy. All had undergone endoscopy for dyspepsia and reported early satiety. Two groups were identified including those with peak duodenal mucosal eosinophil densities above 30/high power field (N = 28) and those below 30 (N = 16). The fasting plasma samples were analyzed by liquid chromatography/high‐resolution mass spectrometry. Significant differences between groups were determined.ResultsThe eosinophilia group demonstrated significant elevations in several gamma‐glutamyl amino acids. The eosinophilia group had elevations of metabolites associated with oxidative stress including glutathione metabolites (cysteinlyglycine and cys‐gly oxidized), and metabolites related to nitric oxide synthesis (arginine, citrulline, ornithine, and dimethylarginine). Eosinophilia was also associated with alterations in lipid metabolism including several long‐chain acylcarnitine conjugated fatty acids. Carnitine levels were lower in the eosinophilia group. Lastly, vanillymandelate, a derivative of norepinephrine and epinephrine was elevated in the eosinophilia group.ConclusionsIn patients with dyspepsia and early satiety, duodenal mucosal eosinophilia is associated with metabolites levels which are consistent with increased oxidative stress and alterations in lipid metabolism. Eosinophilia was also associated with lower carnitine levels. These alterations may contribute to pathophysiology and represent therapeutic targets.

Publisher

Wiley

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