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

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.

Evaluation of expression of common genes in the intestine and peripheral blood mononuclear cells (PBMC) associated with celiac disease.

AIM: this study was conducted to investigate expression of the genes associated with CD in the target tissue in order to estimate contribution of each single gene to development of immune response. Then, the same set of genes was evaluated in peripheral blood mononuclear cells (PBMCs). BACKGROUND: Celiac disease (CD) is a chronic systemic autoimmune disease of the small intestine occurring in genetically-susceptible individuals. There are several genes related to immune response. METHODS: For this purpose, the genes related to CD were extracted from public databases (documents of proteomics and microarray-based techniques) and were organized in a protein-protein interaction network using the search tool for retrieval of interacting genes/proteins (STRING) database as a plugin of Cytoscape software version 3.6.0. The main genes were introduced and enriched via ClueGO to find the related biochemical pathways. The network was analyzed, and the most important genes were introduced based on central indices. RESULTS: Among 20 CD genes as hub and bottleneck nodes, there were 7 genes with common expression in blood and intestinal tissue (C-X-C motif chemokine 11(CXCL11), granzyme B (GZMB), interleukin 15(IL-15), interleukin 17(IL-17A), interleukin 23(IL-23A), t-box transcription factor 21(TBX21), and tumor necrosis factor alpha-induced protein 3(TNFAIP3)). CONCLUSION: The enriched biological process related to the central nodes of celiac network indicated that most of hub-bottleneck genes are the well-known ones involved in different types of autoimmune and inflammatory diseases.