NON‐CELIAC GLUTEN SENSITIVITY (NCGS): IS THE GLUTEN THE TRUE CULPRIT? A CLINICAL AND IMMUNOLOGICAL STUDY ABOUT THE TOLERABILITY OF DIFFERENT WHEAT GRAINS IN NCGS PATIENTS.

    Progetto: Research project

    Dettagli progetto

    Description

    A consistent percentage of the general population consider themselves to be suffering from problems caused by wheat and/or gluten ingestion, even if they do have neither Celiac Disease (CD) nor wheat allergy. These patients very often show Irritable Bowel Syndrome (IBS)-like symptoms and this condition is labeled as "Non-celiac gluten sensitivity" (NCGS). The pathogenesis of NCGS is unclear and it is not sure that the gluten is the real causative agent. This project aims to clarify: 1) if NCGS patients react to the gluten ingestion or to other wheat components and if an ancient variety of wheat - despite its gluten content - can be tolerated by the NCGS patients; 2) if wheat ingestion causes an immune reaction in NCGS patients and, if so, to search for possible immunological markers in the intestinal mucosa and in the peripheral blood; 3) if NCGS patients suffer from liver disorders, as commonly described in celiac disease.

    Layman's description

    A consistent percentage of the general population consider themselves to be suffering from problems caused by wheat and/or gluten ingestion, even if they do have neither Celiac Disease (CD) nor wheat allergy; nevertheless, they exclude wheat and gluten from their diets. Most of these patients report a long clinical history, mainly characterized by gastrointestinal symptoms and they are considered simply suffering from irritable bowel syndrome (IBS). The non-medical specialist press has suggested that "17 million Americans are gluten sensitive" and a study performed in UK revealed that the self-reported prevalence for gluten sensitivity" was 13%, with 3.7% consuming a gluten-free diet. In 2011 an international panel of experts defined "Non-celiac gluten sensitivity" (NCGS) as "a non-allergic and non-autoimmune condition in which the consumption of gluten can lead to symptoms similar to those seen in CD". Up to date, there are very scarce data about the pathogenesis of NCGS and it is not sure that the gluten is the real causative agent. For this reason the label of Non-Celiac Wheat Sensitivity (NCWS) (Carroccio A et al. Gastroenterology 2014) has been proposed instead of NCGS. In fact, other hypotheses have been advanced and scarce preliminary data seem to indicate ancient wheat species could be tolerated by NCGS patients. Furthermore, no biomarkers are nowadays known to pose NCGS diagnosis and no data are known about the liver disorders in these patients. We have preliminary unpublished data which suggest that a percentage of NCGS patients tolerate some kinds of ancient wheat cultivar or the kamut, all grains containing gluten. It is also known that old diploid grass-like species of Triticum, as Triticum monococcum, contain a low number of stimulatory epitopes of T lymphocytes from small intestinal biopsies on CD patients (Molberg O. Gastroenterology 2005) and are clinically tolerated by these patients (Zanini B et al. BMC Gastroenterol 2013). Furthermore, it has been demonstrated that the wheat varieties differ on the basis of the "gluten index", a measure of the gluten polymerization. Some wheat species cultured at the beginning of the 20th century have a much lower gluten index (thus a lower gluten polymerization) than the species currently cultured. It is known that the high gluten polymerization makes difficult the digestive process. As regards the immunological aspects, there is evidence that wheat proteins other than gluten could activate the innate immune system ( Junker Y et al. J. Exp. Med. 2012). Furthermore, there are data which demonstrated a role for the adaptive immunity in NCGS; in fact, an interferon gamma response in duodenal biopsies has been showed after gluten challenge (Brottveit M et al. Am J Gastroenterol 2013). Very recent data from our group showed that, in patients with active NCGS, IFN-gamma-producing Type 1 Innate Lymphoid Cells (ILC1) infiltrate rectal mucosa and, consequently, supported a role for this innate lymphoid cell population in the pathogenesis of NCGS (Clin Transl Gastroenterol 2016). We have demonstrated also that a large percentage of NCGS patients react to other food proteins (Carroccio A et al Am J Gastroenterol 2012) and the hypothesis that a percentage of these patients suffer from multiple food hypersensitivity has been proposed (Carroccio A et al. Am J Gastroenterol 2013).Our first hypothesis is that NCGS patients (or at least a percentage of them) do not react to the gluten ingestion, but that other wheat omponents or characteristics, still unknown, play a role in determining symptoms

    Key findings

    Salute
    StatoFinito
    Data di inizio/fine effettiva1/1/181/1/20