Gastroenterology

Gastroenterology

Volume 148, Issue 6, May 2015, Pages 1195-1204
Gastroenterology

Nonceliac Gluten and Wheat Sensitivity
Nonceliac Gluten Sensitivity

https://doi.org/10.1053/j.gastro.2014.12.049Get rights and content

During the past decade there has been an impressive increase in popularity of the gluten-free diet (GFD)—now the most trendy alimentary habit in the United States and other countries. According to recent surveys, as many as 100 million Americans will consume gluten-free products within a year. Operating under the concept that the GFD benefits only individuals with celiac disease, health care professionals have struggled to separate the wheat from the chaff; there are claims that eliminating gluten from the diet increases health and helps with weight loss, or even that gluten can be harmful to every human being. However, apart from unfounded trends, a disorder related to ingestion of gluten or gluten-containing cereals, namely nonceliac gluten sensitivity (NCGS), has resurfaced in the literature, fueling a debate on the appropriateness of the GFD for people without celiac disease. Although there is clearly a fad component to the popularity of the GFD, there is also undisputable and increasing evidence for NCGS. However, we require a better understanding of the clinical presentation of NCGS, as well as its pathogenesis, epidemiology, management, and role in conditions such as irritable bowel syndrome, chronic fatigue, and autoimmunity. Before we can begin to identify and manage NCGS, there must be agreement on the nomenclature and definition of the disorder based on proper peer-reviewed scientific information. We review the most recent findings on NCGS and outline directions to dissipate some of the confusion related to this disorder.

Section snippets

Definition

Since 2010, the definition of NCGS has been discussed at 3 consensus conferences, which led to 3 publications.13, 14, 15 Given the uncertainties about this clinical entity and the lack of diagnostic biomarkers, all 3 reports concluded that NCGS should be defined by the following exclusionary criteria: a clinical entity induced by the ingestion of gluten leading to intestinal and/or extraintestinal symptoms that resolve once the gluten-containing foodstuff is eliminated from the diet, and when

Clinical Presentation

Symptoms of NCGS usually occur within hours or days after ingestion of gluten-containing grains, and disappear rapidly when these grains are eliminated from the diet. NCGS most frequently produces a combination of intestinal and extraintestinal symptoms. IBS-like symptoms, such as abdominal pain, gas, distension, and irregular bowel movements, frequently are reported and therefore make it difficult to distinguish NCGS from IBS induced by other causes. The differential diagnosis is facilitated

NCGS and IBS: Are They Synonymous?

IBS is a syndrome that appears to be a mixed bag of distinct entities with common clinical presentations. Therefore, it is possible to consider some subjects with NCGS to be typical IBS patients and vice versa: a subgroup of IBS patients may have NCGS. This last scenario was highlighted in subjects affected by the diarrhea-predominant variant of IBS29—particularly those with HLA-DQ2 and/or DQ8 genotypes (associated with celiac disease). In these subjects, ingestion of gluten-containing grains

NCGS and Extraintestinal Symptoms

Some patients with NCGS have disorders such as schizophrenia, autism spectrum disorders, allergies, or autoimmune disorders. GFDs can have positive effects in some of these patients and help them manage NCGS and extraintestinal disorders. Patients with schizophrenia who produced high levels of anti-gliadin IgGs and anti-TG6, but were excluded from having celiac disease, had reduced symptoms on a GFD.34

Many patients with celiac disease also have atopic disorders. Thirty percent of patients’

Epidemiology

Little is known about the prevalence of NCGS in the general population, mainly because many people make a self-diagnosis and start a GFD without medical advice or consultation. However, according to the most recent data, NCGS is not an uncommon disorder. In a region of New Zealand, 5% of children reported non–celiac disease–related avoidance of gluten-containing food.36 Gluten avoidance was associated with improvement of nonspecific behavioral and GI complaints.36 It remains to be determined

Pathogenesis

Researchers are investigating the pathogenesis of NCGS; this disorder only recently has become a subject of systematic research. Our level of knowledge about NCGS pathogenesis is comparable with what was known about celiac disease more than 20 years ago. Gluten is the undisputable cause of celiac disease and therefore it was assumed that the same applied to NCGS. However, besides gluten, wheat, barley, rye, and their derivatives contain other components that induce symptoms, including

Future Directions

NCGS first was described in the early 1970s, but over the past decade the number of patients with NCGS and publications on this topic have increased greatly. However, it is still not clear how to diagnose or manage this condition, and the pathophysiological mechanisms are unclear. Studies in animal models will help researchers to identify, isolate, and characterize compounds that contribute to its development (ATIs, gluten or others), most likely to be found in wheat and related staples. We

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    Conflicts of interest AF is Co-Founder and a stock holder of Alba Therapeutics and receives research fund support from INOVAS Diagnostics. DS holds a patent on the tissue transglutaminase assay. The remaining authors disclose no conflicts.

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