The spectrum of noncoeliac gluten sensitivity

Key Points

  • Individuals are increasingly self-reporting gluten sensitivity and placing themselves on a gluten-free diet outside a diagnosis of coeliac disease or IgE-mediated wheat allergy

  • This clinical entity has been termed noncoeliac gluten sensitivity (NCGS)

  • The symptoms evoked by gluten in NCGS include a constellation of intestinal and extraintestinal symptoms

  • Nongluten components of the grain can also be responsible for triggering symptoms in individuals with NCGS

  • No diagnostic biomarkers to differentiate between gluten and nongluten components currently exist; positive antigliadin antibodies support the diagnosis of NCGS but have limited sensitivity and specificity

  • Patients presenting with NCGS are a heterogeneous group and should be counselled about the uncertainties surrounding their diagnosis


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.

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Figure 1: MRS of the cerebellum in patients with gluten ataxia.
Figure 2: A head MRI of a 55-year-old patient with intractable headaches and positive AGA (gluten encephalopathy), but no evidence of enteropathy.
Figure 3: Proposed effects of wheat-based constituents that trigger clinical symptoms in NCGS.


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Aziz, I., Hadjivassiliou, M. & Sanders, D. The spectrum of noncoeliac gluten sensitivity. Nat Rev Gastroenterol Hepatol 12, 516–526 (2015).

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