Non-celiac gluten sensitivity: Time for sifting the grain

World J Gastroenterol. 2015 Jul 21;21(27):8221-6. doi: 10.3748/wjg.v21.i27.8221.


In the last few years, a new nomenclature has been proposed for the disease induced by the ingestion of gluten, a protein present in wheat, rice, barley and oats. Besides celiac disease and wheat allergy, the most studied forms of gluten-related disorders characterized by an evident immune mechanism (autoimmune in celiac disease and IgE-mediated in wheat allergy), a new entity has been included, apparently not driven by an aberrant immune response: the non-celiac gluten sensitivity (NCGS). NCGS is characterized by a heterogeneous clinical picture with intestinal and extraintestinal symptoms arising after gluten ingestion and rapidly improving after its withdrawal from the diet. The pathogenesis of NCGS is largely unknown, but a mixture of factors such as the stimulation of the innate immune system, the direct cytotoxic effects of gluten, and probably the synergy with other wheat molecules, are clues for the complicated puzzle. In addition, the diagnostic procedures still remain problematic due to the absence of efficient diagnostic markers; thus, diagnosis is based upon the symptomatic response to a gluten-free diet and the recurrence of symptoms after gluten reintroduction with the possibility of an important involvement of a placebo effect. The temporary withdrawal of gluten seems a reasonable therapy, but the timing of gluten reintroduction and the correct patient management approach are have not yet been determined.

Keywords: Celiac disease; Gluten; Gluten sensitivity; Gluten-related disorders; Non-celiac gluten sensitivity.

Publication types

  • Editorial
  • Review

MeSH terms

  • Autoimmune Diseases
  • Celiac Disease / classification
  • Celiac Disease / diagnosis*
  • Celiac Disease / diet therapy
  • Celiac Disease / immunology
  • Diet, Gluten-Free
  • Food Hypersensitivity / classification
  • Food Hypersensitivity / diagnosis*
  • Food Hypersensitivity / diet therapy
  • Food Hypersensitivity / etiology
  • Food Hypersensitivity / immunology
  • Glutens / adverse effects*
  • Glutens / immunology
  • Humans
  • Immunoglobulin E / immunology
  • Predictive Value of Tests
  • Prognosis
  • Risk Factors
  • Terminology as Topic


  • Immunoglobulin E
  • Glutens