Can arginine, glutamate and glutamine serve as surrogates of intestinal mucosal healing in the patients with celiac disease following gluten-free diet? An NMR based metabolomics study.

Celiac disease (CeD) is a chronic small intestinal autoimmune disease initiated by dietary gluten in genetically predisposed individuals. Till date, the only effective treatment for CeD is the gluten-free diet (GFD). However, not all patients achieve full histological recovery despite GFD. Thus, it is crucial to assess the treatment response and improvement in the villous architecture following GFD. Therefore, present study investigated the potential of NMR-based metabolomics for identifying non-invasive biomarkers for assessing treatment response. Comprehensive metabolic profiling of 120 biological samples comprising of small intestinal mucosal biopsies, blood plasmas and urines collected at two time points (before and after 6-8 months of GFD) from CeD patients (n = 20) was carried out using proton NMR spectroscopy. The levels of arginine glutamate, and glutamine were significantly reduced in both intestinal mucosa and blood plasma of CeD patients after GFD compared to their baseline values. These amino acids play an important role in intestinal energy metabolism, and alleviating inflammation, thereby contributing to healing mechanisms of small intestinal mucosa, following GFD. A logistic regression statistical model based on the combination of the above three blood plasma metabolites demonstrated AUC of 0.980, Youden index 0.900 with a sensitivity and a specificity of 90 % and 100 % for monitoring treatment response in CeD patients after GFD. The study revealed a panel of non-invasive plasma biomarkers (arginine, glutamate and glutamine) which may serve as surrogates of mucosal healing and treatment response in CeD patients, however, the findings need to be validated in a large cohort of patients.