Bio-markers of Not-celiac Wheat Sensitivity

Gluten is the most important protein component of some grains, notably wheat, rye, and barley, which are the basis for a variety of wheat-derived alimentary products consumed throughout the world (bread, pasta, pizza etc). However the "engineering" of gluten-containing grains created the conditions for human diseases related to gluten exposure. These forms of gluten intolerance represent a heterogeneous set of conditions, including celiac disease, wheat allergy and gluten sensitivity (GS), that, combined, seems to affect about 10% of the general population. The frequency of not-celiac GS is however still unknown, even though it is possible that this condition have been undiagnosed and under-diagnosed by the physicians for a long time. The immune responsiveness to wheat antigens represents a complex process, and its establishment and maintenance are not completely elucidated. The most frequent diseases caused by wheat ingestion are T cell-mediated disorders, i.e. celiac disease and IgE-mediated allergic reactions. However, besides celiac disease and wheat allergy, there are cases of gluten reactions in which neither autoimmune nor IgE-mediated allergic mechanisms are involved. These are generally defined as GS. Some subjects, who experience symptoms when eating gluten-containing products and show improvement when following a gluten-free diet (GFD), may have GS instead of celiac disease or wheat allergy. GS patients are unable to tolerate gluten and develop an adverse reaction when eating gluten, that, usually, and differently from celiac disease, does not lead to small intestinal damage. Gastrointestinal symptoms in GS patients may resemble those associated with celiac disease, but the overall clinical picture is generally less severe and is not accompanied by the occurrence of autoantibodies (i.e. anti-tTG or EMA) or autoimmune disease (i.e. Hashimoto's thyroiditis). Typically, the diagnosis is made by exclusion, and an elimination diet and an "open challenge" (i.e., the monitored reintroduction of gluten-containing foods) are most often used to evaluate whether health improves or worsen with the elimination or reintroduction of gluten in the diet, respectively. Gluten-sensitivity can cause both gastrointestinal and extra-intestinal symptoms; among the former, the most frequent are IBS-like symptoms including abdominal pain, bloating, diarrhea, constipation and alternate bowel habit. However, as it is not known what component of the cereals causes the symptoms in so called "gluten-sensitive" patients, we prefer to speak of "Not-celiac wheat sensitivity" (NCWS). Furthermore, in our experience, NCWS patients can suffer from multiple food hypersensitivity and need of a more restricted diet with the elimination of cow's milk, egg and other foods, in addition to wheat. For these reasons, before to undergo the gluten challenge, the patients will undergo an oligoantigenic diet.

This study has two major aims:

1. Evaluation of the effective dependence from the wheat of the IBS-like manifestations presented by subjects with suspected NCWS. The study will be done after a period of GFD, comparing two groups of suspected NCWS subjects: administering wheat flour or placebo (for 15 days).

2. Identification of possible markers (serological, biochemical, immunological, histological features, expression of cytokines and other constitutive mucosal proteins from peripheral blood mononuclear cells, mucosal lymphocytes and fecal biomarkers) that may be of help to diagnose the condition of NCWS. In particular, the investigators will search for markers of NCWS in the colon mucosa of the patients with IBS-like symptoms.