Non-celiac gluten sensitivity: All wheat attack is not celiac

Currently, 1% of the United States population holds a diagnosis for celiac disease (CD), however, a more recently recognized and possibly related condition, “non-celiac gluten sensitivity” (NCGS) has been suggested to affect up to 6% of the United States public. While reliable clinical tests for CD exist, diagnosing individuals affected by NCGS is still complicated by the lack of reliable biomarkers and reliance upon a broad set of intestinal and extra intestinal symptoms possibly provoked by gluten. NCGS has been proposed to exhibit an innate immune response activated by gluten and several other wheat proteins. At present, an enormous food industry has developed to supply gluten-free products (GFP) with GFP sales in 2014 approaching $1 billion, with estimations projecting sales to reach $2 billion in the year 2020. The enormous demand for GFP also reflects a popular misconception among consumers that gluten avoidance is part of a healthy lifestyle choice. Features of NCGS and other gluten related disorders (e.g., irritable bowel syndrome) call for a review of current distinctive diagnostic criteria that distinguish each, and identification of biomarkers selective or specific for NCGS. The aim of this paper is to review our current understanding of NCGS, highlighting the remaining challenges and questions which may improve its diagnosis and treatment.

[1]  E. Rimm,et al.  Long term gluten consumption in adults without celiac disease and risk of coronary heart disease: prospective cohort study , 2017, British Medical Journal.

[2]  D. Schuppan,et al.  Nutritional Wheat Amylase-Trypsin Inhibitors Promote Intestinal Inflammation via Activation of Myeloid Cells. , 2017, Gastroenterology.

[3]  W. Willett,et al.  Abstract 11: Associations of Gluten Intake With Type 2 Diabetes Risk and Weight Gain in Three Large Prospective Cohort Studies of US Men and Women , 2017, Circulation.

[4]  A. Carroccio,et al.  Suspected Nonceliac Gluten Sensitivity Confirmed in Few Patients After Gluten Challenge in Double‐Blind, Placebo‐Controlled Trials , 2017, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[5]  G. Caio,et al.  Pathophysiology of non-celiac gluten sensitivity: where are we now? , 2017, Minerva gastroenterologica e dietologica.

[6]  J. Narciso-Schiavon,et al.  To screen or not to screen? Celiac antibodies in liver diseases , 2017, World journal of gastroenterology.

[7]  R. De Giorgio,et al.  Non-coeliac gluten/wheat sensitivity: advances in knowledge and relevant questions , 2017, Expert review of gastroenterology & hepatology.

[8]  C. Isonne,et al.  Intestinal, Systemic, and Oral Gluten-related Alterations in Patients With Nonceliac Gluten Sensitivity , 2016, Journal of clinical gastroenterology.

[9]  A. Nikpoor,et al.  Serum immune biomarkers in irritable bowel syndrome. , 2016, Clinics and research in hepatology and gastroenterology.

[10]  B. Lebwohl,et al.  Nonceliac Gluten Sensitivity. , 2016, Advances in nutrition.

[11]  E. Collyer,et al.  Nonceliac gluten sensitivity: an approach to diagnosis and management , 2016, Current opinion in pediatrics.

[12]  E. Verdú,et al.  Non-coeliac gluten sensitivity: are we closer to separating the wheat from the chaff? , 2016, Gut.

[13]  E. Verna,et al.  Intestinal cell damage and systemic immune activation in individuals reporting sensitivity to wheat in the absence of coeliac disease , 2016, Gut.

[14]  A. Zhernakova,et al.  A novel biomarker panel for irritable bowel syndrome and the application in the general population , 2016, Scientific Reports.

[15]  Bryn Nelson,et al.  To Screen or Not to Screen? , 2023, Endocrinology and metabolism.

[16]  S. Puli,et al.  Irritable Bowel Syndrome: A Clinical Review. , 2016, Current rheumatology reviews.

[17]  L. Pruimboom,et al.  The opioid effects of gluten exorphins: asymptomatic celiac disease , 2015, Journal of Health, Population and Nutrition.

[18]  M. Bardella,et al.  Management of Nonceliac Gluten Sensitivity by Gastroenterology Specialists: Data from an Italian Survey , 2015, BioMed research international.

[19]  Y. Sanz Microbiome and Gluten , 2015, Annals of Nutrition and Metabolism.

[20]  P. Ferranti,et al.  Extensive in vitro gastrointestinal digestion markedly reduces the immune-toxicity of Triticum monococcum wheat: implication for celiac disease. , 2015, Molecular nutrition & food research.

[21]  D. Sanders,et al.  The spectrum of noncoeliac gluten sensitivity , 2015, Nature Reviews Gastroenterology &Hepatology.

[22]  T. Hausken,et al.  Reduction in duodenal endocrine cells in irritable bowel syndrome is associated with stem cell abnormalities. , 2015, World journal of gastroenterology.

[23]  F. Koning,et al.  Randomised clinical study: Aspergillus niger‐derived enzyme digests gluten in the stomach of healthy volunteers , 2015, Alimentary pharmacology & therapeutics.

[24]  D. Schuppan,et al.  Diagnosis of Non-Celiac Gluten Sensitivity (NCGS): The Salerno Experts’ Criteria , 2015, Nutrients.

[25]  G. Barbara,et al.  247 Zonulin Serum Levels Are Increased in Non-Celiac Gluten Sensitivity and Irritable Bowel Syndrome With Diarrhea , 2015 .

[26]  M. Camilleri,et al.  Trends and Racial/Ethnic Disparities in Gluten-Sensitive Problems in the United States: Findings from the National Health and Nutrition Examination Surveys From 1988 to 2012 , 2015, The American Journal of Gastroenterology.

[27]  A. Fasano,et al.  Effect of Gliadin on Permeability of Intestinal Biopsy Explants from Celiac Disease Patients and Patients with Non-Celiac Gluten Sensitivity , 2015, Nutrients.

[28]  Mak Adam Daulatzai,et al.  Non-celiac gluten sensitivity triggers gut dysbiosis, neuroinflammation, gut-brain axis dysfunction, and vulnerability for dementia. , 2015, CNS & neurological disorders drug targets.

[29]  P. Moayyedi,et al.  American College of Gastroenterology Monograph on the Management of Irritable Bowel Syndrome and Chronic Idiopathic Constipation , 2014, The American Journal of Gastroenterology.

[30]  G. Corazza,et al.  An Italian prospective multicenter survey on patients suspected of having non-celiac gluten sensitivity , 2014, BMC Medicine.

[31]  D. Leffler,et al.  Celiac Disease or Non-Celiac Gluten Sensitivity? An Approach to Clinical Differential Diagnosis , 2014, The American Journal of Gastroenterology.

[32]  F. Tovoli,et al.  Effect of gluten free diet on immune response to gliadin in patients with non-celiac gluten sensitivity , 2014, BMC Gastroenterology.

[33]  D. Sanders,et al.  A UK study assessing the population prevalence of self-reported gluten sensitivity and referral characteristics to secondary care , 2014, European journal of gastroenterology & hepatology.

[34]  D. Schuppan,et al.  Non-Celiac Gluten Sensitivity: The New Frontier of Gluten Related Disorders , 2013, Nutrients.

[35]  Jane G Muir,et al.  No effects of gluten in patients with self-reported non-celiac gluten sensitivity after dietary reduction of fermentable, poorly absorbed, short-chain carbohydrates. , 2013, Gastroenterology.

[36]  M. Halushka,et al.  TGFβ Receptor Mutations Impose a Strong Predisposition for Human Allergic Disease , 2013, Science Translational Medicine.

[37]  Christina A. Tennyson,et al.  Prevalence of gluten-free diet adherence among individuals without celiac disease in the USA: results from the Continuous National Health and Nutrition Examination Survey 2009–2010 , 2013, Scandinavian journal of gastroenterology.

[38]  A. Zinsmeister,et al.  A controlled trial of gluten-free diet in patients with irritable bowel syndrome-diarrhea: effects on bowel frequency and intestinal function. , 2013, Gastroenterology.

[39]  K. Lundin,et al.  Mucosal Cytokine Response After Short-Term Gluten Challenge in Celiac Disease and Non-Celiac Gluten Sensitivity , 2013, The American Journal of Gastroenterology.

[40]  T. Libermann,et al.  Wheat amylase trypsin inhibitors drive intestinal inflammation via activation of toll-like receptor 4 , 2012, The Journal of experimental medicine.

[41]  K. Rostami,et al.  Non-coeliac gluten sensitivity , 2012, BMJ : British Medical Journal.

[42]  H. Freeman,et al.  Celiac disease: prevalence, diagnosis, pathogenesis and treatment. , 2012, World journal of gastroenterology.

[43]  M. El-Salhy Irritable bowel syndrome: diagnosis and pathogenesis. , 2012, World journal of gastroenterology.

[44]  F. Tovoli,et al.  Serological Tests in Gluten Sensitivity (Nonceliac Gluten Intolerance) , 2012, Journal of clinical gastroenterology.

[45]  Peter R. Gibson,et al.  Proton Pump Inhibitor Therapy Use Does Not Predispose to Small Intestinal Bacterial Overgrowth , 2011, The American Journal of Gastroenterology.

[46]  Peter HR Green,et al.  Spectrum of gluten-related disorders: consensus on new nomenclature and classification , 2012, BMC Medicine.

[47]  V. Casolaro,et al.  Divergence of gut permeability and mucosal immune gene expression in two gluten-associated conditions: celiac disease and gluten sensitivity , 2011, BMC medicine.

[48]  E. Mayer,et al.  The brain-gut axis in abdominal pain syndromes. , 2011, Annual review of medicine.

[49]  V. Casolaro,et al.  Differential Mucosal IL-17 Expression in Two Gliadin-Induced Disorders: Gluten Sensitivity and the Autoimmune Enteropathy Celiac Disease , 2009, International Archives of Allergy and Immunology.

[50]  M. Zeitz,et al.  Predictors of clinical response to gluten-free diet in patients diagnosed with diarrhea-predominant irritable bowel syndrome. , 2007, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[51]  W. Caspary,et al.  Celiac disease , 2006, Orphanet journal of rare diseases.

[52]  G R Corazza,et al.  The immune recognition of gluten in coeliac disease , 2005, Clinical and experimental immunology.

[53]  T. Thompson Gluten contamination of commercial oat products in the United States. , 2004, The New England journal of medicine.

[54]  R. Hubbard,et al.  Malignancy and mortality in people with coeliac disease: population based cohort study , 2004, BMJ : British Medical Journal.

[55]  P. Roepstorff,et al.  Proteome Analysis of Grain Filling and Seed Maturation in Barley1 , 2002, Plant Physiology.

[56]  L. Greco,et al.  Duration of exposure to gluten and risk for autoimmune disorders in patients with celiac disease. SIGEP Study Group for Autoimmune Disorders in Celiac Disease. , 1999, Gastroenterology.

[57]  H. Heymans,et al.  The daily gluten intake in relatives of patients with coeliac disease compared with that of the general Dutch population , 1997, European journal of gastroenterology & hepatology.

[58]  J. Findling,et al.  Hypocalcemia and skeletal disease as presenting features of celiac disease. , 1997, Archives of internal medicine.

[59]  Ommega Internationals,et al.  Celiac disease: Participation of Cytokines and Other Factors in the Immune Response , 2016 .

[60]  K. Lundin,et al.  Non-celiac gluten sensitivity: a work-in-progress entity in the spectrum of wheat-related disorders. , 2015, Best practice & research. Clinical gastroenterology.

[61]  M. Bardella,et al.  Non-celiac gluten sensitivity: Time for sifting the grain. , 2015, World journal of gastroenterology.

[62]  J. Murray Gluten sensitivity: from gut to brain , 2011 .

[63]  A. Zinsmeister,et al.  FUNCTIONAL BOWEL DISORDERS , 2007, The American Journal of Gastroenterology.

[64]  R. Ferguson,et al.  "Gluten-sensitive diarrhea without evidence of celiac disease". , 1980, Gastroenterology.