The spectrum of noncoeliac gluten sensitivity

Nat Rev Gastroenterol Hepatol. 2015 Sep;12(9):516-26. doi: 10.1038/nrgastro.2015.107. Epub 2015 Jun 30.


The past 5 years have seen an increase in the use of a gluten-free diet outside a diagnosis of coeliac disease or IgE-mediated wheat allergy. This trend has led to the identification of a new clinical entity termed noncoeliac gluten sensitivity (NCGS). In this Review, we discuss the evidence for NCGS as demonstrated by the results of double-blind, placebo-controlled dietary rechallenge studies. Furthermore, the characteristic phenotype of individuals with NCGS is described as well as the symptom manifestations commonly reported after gluten exposure, which include intestinal symptoms consistent with IBS, and extraintestinal symptoms such as neurological dysfunction, psychological disturbances, fibromyalgia and skin rash. Moreover, emerging evidence suggests that NCGS can be associated with organic gastrointestinal pathologies, such as IBD, in which its presence might be a reflection of severe or stricturing disease. However, NCGS is not without its controversies and uncertainties, in particular pertaining to whether it is gluten or nongluten components of the grain evoking symptoms; evidence suggests that fermentable carbohydrates, amylase trypsin inhibitors and wheat-germ agglutinin can also be responsible culprits. Finally, we discuss the novel techniques that might help diagnose NCGS in the future.

Publication types

  • Review

MeSH terms

  • Celiac Disease / diagnosis
  • Diagnosis, Differential
  • Food Hypersensitivity / complications
  • Food Hypersensitivity / diagnosis
  • Food Hypersensitivity / immunology*
  • Glutens / adverse effects*
  • Glutens / immunology*
  • Humans
  • Irritable Bowel Syndrome / immunology
  • Phenotype


  • Glutens