IN THIS ARTICLE
• So what is gluten?
• Selected symptoms of celiac disease
• Selected foods and products containing gluten
Gluten has become a dietary pariah (see “So What Is Gluten?"). The American public’s enthusiasm for a gluten-free diet has spurred a gluten-free food industry that has grown, on average, 34% per year since 2009, with annual sales predicted to reach an impressive $15.5 billion by 2016.1 This trend coincides with the national media’s intense focus on gluten sensitivity (GS), as well as best-selling books such as Wheat Belly and Grain Brain.2,3
Gluten-free food products, once relegated to boutique food shops and limited shelf space, now fill sections in large grocery and drugstore chains. Many restaurants have added gluten-free items to their menus (although gluten-free Big Macs have been available in Finland for more than 20 years).4 Only celiac disease (CD), which affects approximately 1% of the American population, requires strict gluten avoidance; yet more than 30% of US adults report having reduced their gluten intake, most claiming they did so to promote a “healthier” diet or support weight loss.1
PREVALENCE AND PATHOLOGY OF GS DISORDERS
Gluten sensitivity, once used to denote CD alone, now includes a group of gluten-intolerant conditions unrelated to CD—primarily nonceliac gluten sensitivity (NCGS) and wheat allergy (WA)—although the nomenclature is likely to change. While these disorders differ in underlying pathogenesis, each demonstrates a resolution of symptoms when the patient is placed on a gluten-free diet. Of these GS disorders, only NCGS lacks clarity with regard to incidence, diagnosis, and pathology.5
Celiac Disease
Celiac disease is an autoimmune, T-cell–activated disease that manifests in genetically susceptible individuals (with gene variants HLA-DQ2 and HLA-DQ8); it can occur at any age. The incidence of CD in the US has increased from 1 in 500 in 1974 to a current estimate of 1 in 100, although many with CD are believed to be undiagnosed.4,6
CD is the only autoimmune disease for which a trigger is known: gluten. Suspicion for CD should be heightened if the patient or a family member has a history of autoimmune disease. Nearly one-quarter of patients with CD will develop an autoimmune thyroid disorder.7
In CD, a significant enteropathy occurs in response to gluten intake, characterized by inflammation of the proximal small intestine. Individuals with CD produce tissue transglutaminase (tTG) or transglutaminase 2 (TG2) autoantibodies, resulting in gluten-specific CD4+ Th1 T-cell activation and an immune response that causes an upregulation of zonulin.8 Zonulin, a protein that modulates the permeability of the intestinal mucosal wall, is believed to play a role in “leaky gut syndrome” and autoimmune disease. The upregulation of zonulin in CD creates a disruption of the intestinal mucosal lining, causing villous mucosal atrophy and impairment of intestinal permeability and absorption.9
Nonceliac Gluten Sensitivity
NCGS is a poorly understood condition first described in the 1980s and recently “rediscovered” as a gluten-related disorder.10 Its actual prevalence is unknown because of unclear diagnostic criteria but is likely much higher than that of CD.1,4 Unlike CD, there does not appear to be a genetic predisposition for NCGS, nor is it believed to be an autoimmune disorder. However, research does suggest that NCGS may increase the risk for autoimmune diseases, such as Hashimoto thyroiditis. NCGS can occur at any age but appears more commonly in adults than children, and in women than men.4
A small but meticulous 2013 study raised doubt about NCGS as a specific gluten-related disorder.11 The results suggested that NCGS should be viewed as a variant of irritable bowel syndrome (IBS), not triggered by gluten but by poorly absorbed carbohydrates found in wheat known as fructans and galactans, and perhaps by other foods containing fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPS). It is believed those with diarrhea-prone IBS are particularly sensitive to gluten.11 As a result, ardent claims of NCGS and improved health with gluten-free diets in those without CD are often discounted.
More recent research findings refute this conjecture, suggesting that NCGS is likely a reaction to other proteins within the gluten family, such as beta-, gamma-, or omega-gliadin, glutenin, wheat germ agglutinin, gluteomorphin, and deamidated gliadin. Development of GS is believed to be triggered by such factors as intestinal infections, altered microbiota, or food additives.4
In any event, the pathogenesis of NCGS remains unclear, and it does not present with the diagnostic antibodies or inflammatory enteropathy seen in patients with CD. Despite this, NCGS does present with gastrointestinal (GI) and extra-intestinal symptoms similar to those of CD.
Wheat Allergies
Wheat is frequently implicated in food allergies, especially in infants and children. The incidence of WA is not known, although up to 4% of adults and 6% of children are estimated to have food allergies. In WA, there is an IgE antibody–mediated reaction to one or more of the wheat proteins (albumin, gliadin, globulin, gluten) that occurs within minutes to hours after exposure to the offending food. Many children with IgE-mediated allergies may “outgrow” them with time.12
Continue for the clinical presentation of GS >>