Metabolic abnormalities of gastrointestinal mucosa in celiac disease: An in vitro proton nuclear magnetic resonance spectroscopy study

Abstract

Background and aim: Celiac disease (CeD) is a common autoimmune disorder in which ingestion of gluten and related proteins leads to inflammation in the small intestine. Although the histological findings in CeD are characteristic, they are not specific. In this study, proton nuclear magnetic resonance (NMR) spectroscopy was used to investigate the differences in metabolic profile of duodenal mucosal biopsies of patients with CeD and controls to find out the biomarker/s of villous atrophy.

Methods: Duodenal mucosal biopsies were collected from 29 CeD patients (mean age 26.2 ± 10.8 years) and 17 controls (mean age 34.1 ± 11.1 years) and were subjected to proton NMR spectroscopy following perchloric acid extraction. Assignment of metabolite resonances was carried out and their concentrations were determined. For comparison between the groups unpaired t-test/Wilcoxon rank sum test was used. Partial least squares-discriminant analysis was performed to study the clustering behavior of the samples from CeD patients and controls using the Unscrambler 10.2 software.

Results: Partial least squares-discriminant analysis clearly differentiated CeD patients from controls. Significantly higher concentrations of isoleucine, leucine, aspartate, succinate, and pyruvate, and lower concentration of glycerophosphocholine, were observed in the duodenal mucosa of CeD patients compared with controls. The results suggest abnormalities in glycolysis, Krebs cycle (energy deficiency), and amino acid metabolism, which may affect the biosynthetic pathways and consequently contribute to villous atrophy.

Conclusions: NMR spectroscopy with multivariate analysis of duodenal mucosal biopsies revealed a characteristic metabolic profile in CeD patients. The work provided an insight in determining biomarker/s for villous atrophy and diagnosis of CeD patients.

Keywords: aspartate; biomarker; duodenal mucosal biopsies; in vitro proton nuclear magnetic resonance spectroscopy; metabonomics; villous atrophy.