title: Non-coeliac gluten/wheat sensitivity: advances in knowledge and relevant questions.
abstract: Non-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.
authors.affiliation: 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.
authors.forename: Umberto
authors.initials: U
authors.lastname: Volta
authors.affiliation: 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.|b Mucosal Immunology and Biology Research Center, Massachusetts General Hospital , Harvard Medical School , Boston , USA.
authors.forename: Giacomo
authors.initials: G
authors.lastname: Caio
authors.affiliation: 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.
authors.forename: Tennekoon B
authors.initials: TB
authors.lastname: Karunaratne
authors.affiliation: c Department of Medicine , Columbia University Medical Center , New York , NY , USA.|d Celiac Disease Center , Columbia University Medical Center , New York , NY , USA.|e Institute of Human Nutrition , Columbia University Medical Center , New York , NY , USA.
authors.forename: Armin
authors.initials: A
authors.lastname: Alaedini
authors.affiliation: 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.
authors.forename: Roberto
authors.initials: R
authors.lastname: De Giorgio
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D002446:Celiac Disease / Q000097:blood / Q000175:diagnosis / Q000178:diet therapy / Q000276:immunology; D003937:Diagnosis, Differential; D055050:Diet, Gluten-Free; D005983:Glutens / Q000009:adverse effects* / Q000276:immunology; D006801:Humans; D007159:Immunologic Tests; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D011237:Predictive Value of Tests; D012307:Risk Factors; D014908:Triticum / Q000009:adverse effects* / Q000276:immunology; D021182:Wheat Hypersensitivity / Q000097:blood / Q000175:diagnosis / Q000178:diet therapy / Q000276:immunology
chemical_list: D015415:Biomarkers; D005983:Glutens
keywords: Biomarkers; adaptive immunity; gut microbiome; innate immunity; intestinal epithelial barrier; non-coeliac gluten sensitivity; wheat sensitivity