• Umberto Volta, Giacomo Caio, Tennekoon B Karunaratne, Armin Alaedini, and Roberto De Giorgio.
• a Departments of Medical and Surgical Sciences and Digestive System, Centro di Ricerca Biomedica Applicata (C.R.B.A.) , University of Bologna, St. Orsola-Malpighi Hospital , Bologna , Italy.
• Expert Rev Gastroenterol Hepatol. 2017 Jan 1; 11 (1): 9-18.

IntroductionNon-coeliac gluten/wheat sensitivity (NCG/WS) is a syndrome characterized by intestinal and extra-intestinal symptoms occurring a few hours or days after the ingestion of gluten and wheat proteins in patients testing negative for coeliac disease and wheat allergy. Areas covered: The present review deals with recent scientific acquisitions of this gluten-related syndrome, including pathogenetic mechanisms, clinical picture, symptom score, biomarkers and double-blind placebo-controlled trial for diagnosis, and treatment. The methodology used was a literature search on NCG/WS using Medline and Premedline from 1970 to August 2016. Expert commentary: We discussed the pathogenesis of symptom generation and altered gut physiology in NCG/WS. Possible mechanisms include innate and adaptive immune activation, impaired intestinal epithelial barrier and changes in gut microbiome. These interlinked factors may be exploited for their clinical relevance as possible biomarkers. A systemic immune response to microbial and wheat antigens, together with intestinal cell damage, occurs in patients with NCG/WS. Due to the lack of established biomarkers, it is mandatory to validate the diagnosis of the syndrome by means of a well-defined work-up involving dietary challenge. Finally, dietary and other therapeutic indications have been thoroughly reviewed.

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