Non-coeliac gluten/wheat sensitivity: advances in knowledge and relevant questions

Expert Rev Gastroenterol Hepatol. 2017 Jan;11(1):9-18. doi: 10.1080/17474124.2017.1260003. Epub 2016 Nov 23.


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.

Keywords: Biomarkers; adaptive immunity; gut microbiome; innate immunity; intestinal epithelial barrier; non-coeliac gluten sensitivity; wheat sensitivity.

Publication types

  • Review

MeSH terms

  • Animals
  • Biomarkers / blood
  • Celiac Disease / blood
  • Celiac Disease / diagnosis
  • Celiac Disease / diet therapy
  • Celiac Disease / immunology
  • Diagnosis, Differential
  • Diet, Gluten-Free
  • Glutens / adverse effects*
  • Glutens / immunology
  • Humans
  • Immunologic Tests
  • Intestinal Mucosa* / immunology
  • Intestinal Mucosa* / metabolism
  • Intestinal Mucosa* / pathology
  • Predictive Value of Tests
  • Risk Factors
  • Triticum / adverse effects*
  • Triticum / immunology
  • Wheat Hypersensitivity* / blood
  • Wheat Hypersensitivity* / diagnosis
  • Wheat Hypersensitivity* / diet therapy
  • Wheat Hypersensitivity* / immunology


  • Biomarkers
  • Glutens