Screening of Altered Metabolites and Metabolic Pathways in Celiac Disease Using NMR Spectroscopy.

Ensieh Khalkhal,Amir Taherkhani,Mohammad Hossain Haidari,B Fatemeh Nobakht M Gh,Mostafa Rezaei-Tavirani,Mohammad Rostami-Nejad,Fariba Fathi,Nastaran Asri,Alka Singh

doi:10.1155/2021/1798783

Abstract

Background Celiac disease (CeD) is an autoimmune intestinal disorder caused by gluten protein consumption in genetically predisposed individuals. As biopsy sampling is an invasive procedure, finding novel noninvasive serological markers for screening of at-risk CeD population is a priority. Metabolomics is helpful in monitoring metabolite changes in body fluids and tissues. In the present study, we evaluated serum metabolite levels of CeD patients relative to healthy controls with the aim of introducing new biomarkers for population screening. Method We compared the serum metabolic profile of CeD patients (n = 42) and healthy controls (n = 22) using NMR spectroscopy and multivariate analysis. Result 25 metabolites were identified by serum metabolic profiling. Levels of 3-hydroxyisobutyric acid and isobutyrate showed significant differences in CeD patients' samples compared with healthy controls (p < 0.05). According to pathway analysis, our data demonstrated that changes in nine metabolic pathways were significantly disrupted/affected in patients with CeD. These enriched pathways are involved in aminoacyl-tRNA biosynthesis; primary bile acid biosynthesis; nitrogen metabolism; glutamine and glutamate metabolism; valine, leucine, and isoleucine biosynthesis and degradation; taurine and hypotaurine metabolism; glyoxylate and dicarboxylate metabolism; glycine, serine, and threonine metabolism; and arginine biosynthesis. Conclusion In summary, our results demonstrated that changes in the serum level of 25 metabolites may be useful in distinguishing CeD patients from healthy controls, which have the potential to be considered candidate biomarkers of CeD.

Highlights

Celiac disease (CeD), an autoimmune intestinal disorder that affects up to 1% of the world population, is caused by the ingestion of gluten in genetically predisposed individuals carrying HLA-DQ2 or HLADQ8 [1,2,3]
After Nuclear magnetic resonance (NMR) spectral preprocessing, the resulting binned data including 64 samples and 408 variables were analyzed by unsupervised Principal component analysis (PCA) to find patterns, trends, and outliers
PCA score plots showed that the CeD group is not separated clearly from the healthy control group (R2X: 0.817; Q2: 0.58) (Figure 1(a))

Summary

Introduction

Celiac disease (CeD), an autoimmune intestinal disorder that affects up to 1% of the world population, is caused by the ingestion of gluten (found in wheat, barley, and rye) in genetically predisposed individuals carrying HLA-DQ2 or HLADQ8 [1,2,3]. Metabolomics can describe the biological changes by monitoring metabolites in body fluids and tissues and improve the understanding of the main mechanisms behind diseases. It can help in the discovery of potential prognostic and diagnostic biomarkers of disease by describing biological changes between the target and control groups and give a cell physiology snapshot by metabolic profiling determination. We evaluated serum metabolite levels of CeD patients relative to healthy controls with the aim of introducing new biomarkers for population screening. Our results demonstrated that changes in the serum level of 25 metabolites may be useful in distinguishing CeD patients from healthy controls, which have the potential to be considered candidate biomarkers of CeD

Methods

Results

Conclusion