Characterization of mouse models to study the pathogenesis of celiac disease and the role played by the dysregulation of the intestinal microbiota

Celiac disease (CD) is a permanent intolerance to dietary protein, gluten, from wheat rye and barley. It occurs in about 1% worldwide population, in genetically predisposed individuals bearing human leukocyte antigen DQ2/DQ8. Although gut epithelial cell stress and the innate immune activation are responsible for the breaking oral tolerance to gliadin, the gluten component, the exact mechanisms through which gliadin can stimulate CD onset are still unclear. Here I show how is important to identify in vivo preclinical models of CD to study its pathogenesis, at molecular level. The increasing prevalence of positive serological marker of CD in Cystic Fibrosis (CF) affected patients let to the hypothesis of a link between the two disorders. Results from my studies indicate that CFTR is potentially involved in the pathogenesis of CD, with gliadin peptides inhibiting CFTR activity and expression. Today, the only treatment for CD is a long-term gluten-free diet. Several evidences show that an altered composition of the intestinal microbiota could play a key role in the pathogenesis of CD, through the modulation of intestinal permeability and the regulation of the immune system. Indeed, although further studies are still required to unveil the molecular mechanisms, results reported in the present work clearly indicate that rebalancing the gut microbiota composition by probiotics administration might represent a new strategy to treat CD affected patients.