An explorative study identifies miRNA signatures for the diagnosis of non-celiac wheat sensitivity

Abstract

Non-celiac wheat sensitivity (NCWS), also referred to as non-celiac gluten sensitivity, is a recently described disorder triggered by wheat/gluten ingestion. NCWS elicits a wide range of symptoms including diarrhoea, intestinal discomfort, and fatigue in analogy with other wheat/gluten-related disorders and celiac disease in particular. From the pathological standpoint, NCWS patients only have a slight increase of intraepithelial lymphocytes, while antibodies to tissue transglutaminase (tTG) and villous atrophy, otherwise diagnostic features of celiac disease, are absent. To date, the diagnosis of NCWS relies on symptoms and exclusion of confounding diseases, since biomarkers are not yet available. Here, the expression levels of selected miRNAs were examined in duodenal biopsies and peripheral blood leukocytes collected from newly diagnosed patients with NCWS and, as controls, from patients with celiac disease and gluten-independent gastrointestinal problems. We identified a few miRNAs whose expression is higher in the intestinal mucosa of patients affected by NCWS in comparison to control patients affect by gluten-independent dyspeptic symptoms (Helicobacter pylori-negative) and celiac disease. The present study provided the first evidence that NCWS patients have a characteristic miRNA expression patterns, such peculiarity could be exploited as a biomarker to the diagnosis of this disease.

Non-Celiac Gluten/Wheat Sensitivity: Clinical Characteristics and Microbiota and Mycobiota Composition by Response to the Gluten Challenge Test

“…The pathogenesis of NCGS/WS is still uncertain; a higher intestinal expression of toll-like receptors suggesting a stronger implication of the innate immune mechanisms, the infiltration of immune cells in the gut mucosa, increased expression of antibodies, and dysregulated gene expression profiling and epigenetic mechanisms have been described [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 ]. Furthermore, impaired intestinal barrier and permeability and gut dysbiosis have been advocated as key factors by several studies [ 1 , 2 , 4 , 10 , 11 ].…”

“…Furthermore, the double-blind placebo-controlled (DBPC) crossover gluten challenge test, which remains at present the gold standard test for NCGS/WS diagnosis, is cumbersome and not easy to perform in daily clinical practice. Indeed, many studies referred to self-reported diagnosis [ 3 , 9 , 10 , 13 , 17 ], but only 8% to 34% of the individuals with self-reported gluten sensitivity worsened their symptoms after gluten ingestion, thus suggesting that self-reporting overemphasized the syndrome [ 18 , 19 , 20 , 21 , 22 ].…”

Beyond the HLA Genes in Gluten-Related Disorders

“…In a recent study by our laboratory we identified seven miRNA (hsa-miR-19b-3p, hsa-miR-19a-3p, hsa-miR-186-5p, hsa-miR-17-5p, hsa-miR-145-5p, hsa-miR-30e-5p, and hsa-miR-143-3p) whose expression was higher in the intestinal mucosa of NCWS patients than in controls with dyspeptic symptoms or celiac disease ( 60 ). Remarkably, six of these miRNA were also dysregulated in peripheral blood leukocytes of NCWS.…”

Is Gluten the Only Culprit for Non-Celiac Gluten/Wheat Sensitivity?

“…Furthermore, evidence was provided for an overexpression of selected miRNA in the intestinal mucosa and peripheral blood leukocytes (PBLs) of NCWS patients if compared to symptomatic controls with functional dyspepsia or CD. Hsa-miR-30e-5p proved to be the best predictor of NCWS vs. CD in biopsies and vs. controls in PBLs [ 154 ]. The absence of validated diagnostic criteria also explains the high rate of self-diagnosis [ 155 , 156 ] as well as the impact of patients’ perception of symptoms and of the nocebo effect on the interpretation of study results [ 157 ].…”