Skip to main content Skip to main navigation menu Skip to site footer
Published: 06-03-2022

Sensibilidade não-celíaca ao glúten

Clinica Lapinha Spa Médico, Lapa, PR, Brazil
non-celiac gluten sensitivity sensitivity to gluten sensitivity to wheat gluten-related diseases gluten-free diet gluten wheat


Among adverse food reactions, gluten-related disorders are now gaining more and more space in scientific and non-scientific publications. These disorders are divided into three entities: celiac disease (CD), wheat allergy (WA), and non-celiac sensitivity to gluten or wheat (NCGS), considering that this cereal is associated more frequently with the manifestations, and since it is also discussed whether or not this grain would be the real triggering food component. Celiac disease is an autoimmune enteropathy, whereas WA is a hypersensitive reaction, mediated or not mediated by immunoglobulin E (IgE). Non-celiac sensitivity to gluten or wheat is an emerging entity of pathophysiology still under discussion, which several researchers propose as a diagnosis of exclusion in relation to CD and WA, and it has aroused great popular excitement and controversy in medical circles. The present review aims to approach NCGS, seeking to distinguish elements of the other two disorders, such as clinical characteristics, differential diagnosis, pathophysiology, and treatment. In many studies, the possibility of overlapping or of diagnostic confusion with other functional gastrointestinal diseases, such as irritable bowel syndrome (IBS) and fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs), is highlighted. We conclude that NCGS, although it is a clinical entity recognized by a significant number of researchers, is still widely questioned regarding its characterization, diagnosis and pathophysiology. This, given the high prevalence estimated and the popular repercussions, is undoubtedly a subject worthy of further and well-conducted studies.


Metrics Loading ...


  1. Ribeiro M, Nunes-Miranda JD, Branlard G, Carrillo JM, Rodriguez-Quijano M, Igrejas G. One hundred years of grain omics: identifying the glutens that feed the world. J Proteome Res 2013; 12 (11) 4702-4716
  2. Barro F, Iehisa JC, Giménez MJ. , et al. Targeting of prolamins by RNAi in bread wheat: effectiveness of seven silencing-fragment combinations for obtaining lines devoid of coeliac disease epitopes from highly immunogenic gliadins. Plant Biotechnol J 2016; 14 (03) 986-996
  3. Gasbarrini G, Mangiola F. Wheat-related disorders: A broad spectrum of ‘evolving’ diseases. United European Gastroenterol J 2014; 2 (04) 254-262
  4. Watkins RD, Zawahir S. Celiac Disease and Nonceliac Gluten Sensitivity. Pediatr Clin North Am 2017; 64 (03) 563-576
  5. , acesso em 29 de outubro de 2017, Raithel, 2016
  6. Aziz I, Dwivedi K, Sanders DS. From coeliac disease to noncoeliac gluten sensitivity; should everyone be gluten free?. Curr Opin Gastroenterol 2016; 32 (02) 120-127
  7. Lionetti E, Pulvirenti A, Vallorani M. , et al. Re-challenge Studies in Non-celiac Gluten Sensitivity: A Systematic Review and Meta-Analysis. Front Physiol 2017; 8: 621
  8. Jericho H, Assiri A, Guandalini S. Celiac Disease and Wheat Intolerance Syndrome: A Critical Update and Reappraisal. J Pediatr Gastroenterol Nutr 2017; 64 (01) 15-21
  9. Collyer EM, Kaplan BS. Nonceliac gluten sensitivity: an approach to diagnosis and management. Curr Opin Pediatr 2016; 28 (05) 638-643
  10. Carroccio A, Giambalvo O, Blasca F, Iacobucci R, D'Alcamo A, Mansueto P. Self-Reported Non-Celiac Wheat Sensitivity in High School Students: Demographic and Clinical Characteristics. Nutrients 2017; 9 (07) E771
  11. Potter M, Walker MM, Talley NJ. Non-coeliac gluten or wheat sensitivity: emerging disease or misdiagnosis?. Med J Aust 2017; 207 (05) 211-215
  12. Volta U, Caio G, Karunaratne TB, Alaedini A, De Giorgio R. Non-coeliac gluten/wheat sensitivity: advances in knowledge and relevant questions. Expert Rev Gastroenterol Hepatol 2017; 11 (01) 9-18
  13. Marchioni Beery RM, Birk JW. Wheat-related disorders reviewed: making a grain of sense. Expert Rev Gastroenterol Hepatol 2015; 9 (06) 851-864
  14. Ortiz C, Valenzuela R, Lucero A Y. [Celiac disease, non celiac gluten sensitivity and wheat allergy: comparison of 3 different diseases triggered by the same food]. Rev Chil Pediatr 2017; 88 (03) 417-423
  15. Vaquero L, Alvarez-Cuenllas B, Rodríguez-Martín L. , et al. [A review of diseases related to the intake of gluten]. Nutr Hosp 2015; 31 (06) 2359-2371
  16. Sapone A, Bai JC, Ciacci C. , et al. Spectrum of gluten-related disorders: consensus on new nomenclature and classification. BMC Med 2012; 10: 13
  17. Jackson JR, Eaton WW, Cascella NG, Fasano A, Kelly DL. Neurologic and psychiatric manifestations of celiac disease and gluten sensitivity. Psychiatr Q 2012; 83 (01) 91-102
  18. Gasbarrini G, Miele L, Corazza GR, Gasbarrini A. When was celiac disease born?: the Italian case from the archeologic site of Cosa. J Clin Gastroenterol 2010; 44 (07) 502-503
  19. Mansueto P, Seidita A, D'Alcamo A, Carroccio A. Non-celiac gluten sensitivity: literature review. J Am Coll Nutr 2014; 33 (01) 39-54
  20. Ellis A, Linaker BD. Non-coeliac gluten sensitivity?. Lancet 1978; 1 (8078): 1358-1359
  21. Cooper BT, Holmes GK, Ferguson R, Thompson RA, Allan RN, Cooke WT. Gluten-sensitive diarrhea without evidence of celiac disease. Gastroenterology 1980; 79 (5 Pt 1): 801-806
  22. Fasano A, Sapone A, Zevallos V, Schuppan D. Nonceliac gluten sensitivity. Gastroenterology 2015; 148 (06) 1195-1204
  23. Leonard MM, Sapone A, Catassi C, Fasano A. Celiac Disease and Nonceliac Gluten Sensitivity: A Review. JAMA 2017; 318 (07) 647-656
  24. Aziz I, Hadjivassiliou M, Sanders DS. The spectrum of noncoeliac gluten sensitivity. Nat Rev Gastroenterol Hepatol 2015; 12 (09) 516-526
  25. Raithel M, Kluger AK, Dietz B, Hetterich U. [Non-allergic gluten sensitivity. A controversial disease - or not yet sufficiently explored?]. Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz 2016; 59 (07) 821-826
  26. Soares FL, de Oliveira Matoso R, Teixeira LG. , et al. Gluten-free diet reduces adiposity, inflammation and insulin resistance associated with the induction of PPAR-alpha and PPAR-gamma expression. J Nutr Biochem 2013; 24 (06) 1105-1111
  27. Biesiekierski JR. What is gluten?. J Gastroenterol Hepatol 2017; 32 (Suppl. 01) 78-81
  28. Frazer AC, Fletcher RF, Ross CA, Shaw B, Sammons HG, Schneider R. Gluten-induced enteropathy: the effect of partially digested gluten. Lancet 1959; 2 (7097): 252-255
  29. Bucci C, Zingone F, Russo I. , et al. Gliadin does not induce mucosal inflammation or basophil activation in patients with nonceliac gluten sensitivity. Clin Gastroenterol Hepatol 2013; 11 (10) 1294-1299.e1
  30. Thies F, Masson LF, Boffetta P, Kris-Etherton P. Oats and bowel disease: a systematic literature review. Br J Nutr 2014; 112 (Suppl. 02) S31-S43
  31. Comino I, Moreno MdeL, Sousa C. Role of oats in celiac disease. World J Gastroenterol 2015; 21 (41) 11825-11831
  32. acesso em 22/10/ 2017
  33. Benoit L, Masiri J, Del Blanco IA, Meshgi M, Gendel SM, Samadpour M. Assessment of Avenins from Different Oat Varieties Using R5-Based Sandwich ELISA. J Agric Food Chem 2017; 65 (08) 1467-1472
  34. Sharma GM, Rallabhandi P, Williams KM, Pahlavan A. Characterization of Antibodies for Grain-Specific Gluten Detection. J Food Sci 2016; 81 (03) T810-T816
  35. Rallabhandi P, Sharma GM, Pereira M, Williams KM. Immunological characterization of the gluten fractions and their hydrolysates from wheat, rye and barley. J Agric Food Chem 2015; 63 (06) 1825-1832
  36. , acesso em outubro de 2017
  37. Sey MS, Parfitt J, Gregor J. Prospective study of clinical and histological safety of pure and uncontaminated Canadian oats in the management of celiac disease. JPEN J Parenter Enteral Nutr 2011; 35 (04) 459-464
  38. Koerner TB, Cléroux C, Poirier C, Cantin I, Alimkulov A, Elamparo H. Gluten contamination in the Canadian commercial oat supply. Food Addit Contam Part A Chem Anal Control Expo Risk Assess 2011; 28 (06) 705-710
  39. Pulido OM, Gillespie Z, Zarkadas M. , et al. Introduction of oats in the diet of individuals with celiac disease: a systematic review. Adv Food Nutr Res 2009; 57: 235-285
  40. de Souza MC, Deschênes ME, Laurencelle S, Godet P, Roy CC, Djilali-Saiah I. Pure Oats as Part of the Canadian Gluten-Free Diet in Celiac Disease: The Need to Revisit the Issue. Can J Gastroenterol Hepatol 2016; 2016: 1576360
  41. Fric P, Gabrovska D, Nevoral J. Celiac disease, gluten-free diet, and oats. Nutr Rev 2011; 69 (02) 107-115
  42. Comino I, Real A, de Lorenzo L. , et al. Diversity in oat potential immunogenicity: basis for the selection of oat varieties with no toxicity in coeliac disease. Gut 2011; 60 (07) 915-922
  43. Giménez MJ, Real A, García-Molina MD, Sousa C, Barro F. Characterization of celiac disease related oat proteins: bases for the development of high quality oat varieties suitable for celiac patients. Sci Rep 2017; 7: 42588
  44. Maglio M, Mazzarella G, Barone MV. , et al. Immunogenicity of two oat varieties, in relation to their safety for celiac patients. Scand J Gastroenterol 2011; 46 (10) 1194-1205
  45. Richman E. The safety of oats in the dietary treatment of coeliac disease. Proc Nutr Soc 2012; 71 (04) 534-537
  46. Araya M, Bascuñán K. Enfermedad celíaca. Una mirada actual. Rev Chil Pediatr 2014; 85 (06) 658-665
  47. Mickowska B, Litwinek D, Gambuś H. Oat raw materials and bakery products - amino acid composition and celiac immunoreactivity. Acta Sci Pol Technol Aliment 2016; 15 (01) 89-97
  48. Real A, Comino I, de Lorenzo L. , et al. Molecular and immunological characterization of gluten proteins isolated from oat cultivars that differ in toxicity for celiac disease. PLoS One 2012; 7 (12) e48365
  49. Uhde M, Ajamian M, Caio G. , et al. Intestinal cell damage and systemic immune activation in individuals reporting sensitivity to wheat in the absence of coeliac disease. Gut 2016; 65 (12) 1930-1937
  50. Tonutti E, Bizzaro N. Diagnosis and classification of celiac disease and gluten sensitivity. Autoimmun Rev 2014; 13 (4-5): 472-476
  51. Catassi C, Elli L, Bonaz B. , et al. Diagnosis of Non-Celiac Gluten Sensitivity (NCGS): The Salerno Experts' Criteria. Nutrients 2015; 7 (06) 4966-4977
  52. Ludvigsson JF, Leffler DA, Bai JC. , et al. The Oslo definitions for coeliac disease and related terms. Gut 2013; 62 (01) 43-52
  53. Krigel A, Lebwohl B. Nonceliac Gluten Sensitivity. Adv Nutr 2016; 7 (06) 1105-1110
  54. Di Sabatino A, Corazza GR. Nonceliac gluten sensitivity: sense or sensibility?. Ann Intern Med 2012; 156 (04) 309-311
  55. Vazquez-Roque M, Oxentenko AS. Nonceliac Gluten Sensitivity. Mayo Clin Proc 2015; 90 (09) 1272-1277
  56. Molina-Infante J, Santolaria S, Sanders DS, Fernández-Bañares F. Systematic review: noncoeliac gluten sensitivity. Aliment Pharmacol Ther 2015; 41 (09) 807-820
  57. Czaja-Bulsa G. Non coeliac gluten sensitivity - A new disease with gluten intolerance. Clin Nutr 2015; 34 (02) 189-194
  58. Elli L, Branchi F, Tomba C. , et al. Diagnosis of gluten related disorders: Celiac disease, wheat allergy and non-celiac gluten sensitivity. World J Gastroenterol 2015; 21 (23) 7110-7119
  59. Guandalini S, Polanco I. Nonceliac gluten sensitivity or wheat intolerance syndrome?. J Pediatr 2015; 166 (04) 805-811
  60. Shahbazkhani B, Sadeghi A, Malekzadeh R. , et al. Non-Celiac Gluten Sensitivity Has Narrowed the Spectrum of Irritable Bowel Syndrome: A Double-Blind Randomized Placebo-Controlled Trial. Nutrients 2015; 7 (06) 4542-4554
  61. Navarro E, Araya M. Sensibilidad no celíaca al gluten: Una patología más que responde al gluten. Rev Med Chil 2015; 143 (05) 619-626
  62. Gibson PR. Food intolerance in functional bowel disorders. J Gastroenterol Hepatol 2011; 26 (Suppl. 03) 128-131
  63. Sapone A, Lammers KM, Casolaro V. , et al. Divergence of gut permeability and mucosal immune gene expression in two gluten-associated conditions: celiac disease and gluten sensitivity. BMC Med 2011; 9: 23
  64. Galipeau HJ, Verdu EF. Gut microbes and adverse food reactions: Focus on gluten related disorders. Gut Microbes 2014; 5 (05) 594-605
  65. Escudero-Hernández C, Peña AS, Bernardo D. Immunogenetic Pathogenesis of Celiac Disease and Non-celiac Gluten Sensitivity. Curr Gastroenterol Rep 2016; 18 (07) 36
  66. Nijeboer P, Bontkes HJ, Mulder CJ, Bouma G. Non-celiac gluten sensitivity. Is it in the gluten or the grain?. J Gastrointestin Liver Dis 2013; 22 (04) 435-440
  67. Schuppan D, Pickert G, Ashfaq-Khan M, Zevallos V. Non-celiac wheat sensitivity: differential diagnosis, triggers and implications. Best Pract Res Clin Gastroenterol 2015; 29 (03) 469-476
  68. Cuccioloni M, Mozzicafreddo M, Bonfili L. , et al. Interfering with the high-affinity interaction between wheat amylase trypsin inhibitor CM3 and toll-like receptor 4: in silico and biosensor-based studies. Sci Rep 2017; 7 (01) 13169
  69. Zevallos VF, Raker V, Tenzer S. , et al. Nutritional Wheat Amylase-Trypsin Inhibitors Promote Intestinal Inflammation via Activation of Myeloid Cells. Gastroenterology 2017; 152 (05) 1100-1113.e12
  70. Hollon J, Puppa EL, Greenwald B, Goldberg E, Guerrerio A, Fasano A. Effect of gliadin on permeability of intestinal biopsy explants from celiac disease patients and patients with non-celiac gluten sensitivity. Nutrients 2015; 7 (03) 1565-1576
  71. Drago S, El Asmar R, Di Pierro M. , et al. Gliadin, zonulin and gut permeability: Effects on celiac and non-celiac intestinal mucosa and intestinal cell lines. Scand J Gastroenterol 2006; 41 (04) 408-419
  72. Brottveit M, Beitnes AC, Tollefsen S. , et al. Mucosal cytokine response after short-term gluten challenge in celiac disease and non-celiac gluten sensitivity. Am J Gastroenterol 2013; 108 (05) 842-850
  73. Wahnschaffe U, Ullrich R, Riecken EO, Schulzke JD. Celiac disease-like abnormalities in a subgroup of patients with irritable bowel syndrome. Gastroenterology 2001; 121 (06) 1329-1338
  74. Francavilla R, Cristofori F, Castellaneta S. , et al. Clinical, serologic, and histologic features of gluten sensitivity in children. J Pediatr 2014; 164 (03) 463-7.e1
  75. Quirce S, Boyano-Martínez T, Díaz-Perales A. Clinical presentation, allergens, and management of wheat allergy. Expert Rev Clin Immunol 2016; 12 (05) 563-572
  76. Ribi C. [Non-celiac wheat sensitivity - growing evidence for a wheat-dependent immune-mediated disease]. Rev Med Suisse 2017; 13 (544-545): 16-17
  77. Kabbani TA, Vanga RR, Leffler DA. , et al. Celiac disease or non-celiac gluten sensitivity? An approach to clinical differential diagnosis. Am J Gastroenterol 2014; 109 (05) 741-746 , quiz 747
  78. Cuomo R, Andreozzi P, Zito FP, Passananti V, De Carlo G, Sarnelli G. Irritable bowel syndrome and food interaction. World J Gastroenterol 2014; 20 (27) 8837-8845
  79. Biesiekierski JR, Peters SL, Newnham ED, Rosella O, Muir JG, Gibson PR. No effects of gluten in patients with self-reported non-celiac gluten sensitivity after dietary reduction of fermentable, poorly absorbed, short-chain carbohydrates. Gastroenterology 2013; 145 (02) 320-8.e1 , 3
  80. El-Salhy M, Hatlebakk JG, Gilja OH, Hausken T. The relation between celiac disease, nonceliac gluten sensitivity and irritable bowel syndrome. Nutr J 2015; 14: 92
  81. Makharia A, Catassi C, Makharia GK. The Overlap between Irritable Bowel Syndrome and Non-Celiac Gluten Sensitivity: A Clinical Dilemma. Nutrients 2015; 7 (12) 10417-10426
  82. Mearin F, Montoro M. [Irritable bowel syndrome, celiac disease and gluten]. Med Clin (Barc) 2014; 143 (03) 124-129
  83. Elli L, Tomba C, Branchi F. , et al. Evidence for the Presence of Non-Celiac Gluten Sensitivity in Patients with Functional Gastrointestinal Symptoms: Results from a Multicenter Randomized Double-Blind Placebo-Controlled Gluten Challenge. Nutrients 2016; 8 (02) 84
  84. Arranz E, Ferguson A. Intestinal antibody pattern of celiac disease: occurrence in patients with normal jejunal biopsy histology. Gastroenterology 1993; 104 (05) 1263-1272
  85. Vázquez-Roque MI, Camilleri M, Smyrk T. , et al. A controlled trial of gluten-free diet in patients with irritable bowel syndrome-diarrhea: effects on bowel frequency and intestinal function. Gastroenterology 2013; 144 (05) 903-911.e3
  86. Dimidi E, Rossi M, Whelan K. Irritable bowel syndrome and diet: where are we in 2018?. Curr Opin Clin Nutr Metab Care 2017; 20 (06) 456-463
  87. Khoshbaten M, Rostami Nejad M, Sharifi N. , et al. Celiac disease in patients with chronic psychiatric disorders. Gastroenterol Hepatol Bed Bench 2012; 5 (02) 90-93
  88. Eaton WW, Byrne M, Ewald H. , et al. Association of schizophrenia and autoimmune diseases: linkage of Danish national registers. Am J Psychiatry 2006; 163 (03) 521-528
  89. West J, Logan RF, Hubbard RB, Card TR. Risk of schizophrenia in people with coeliac disease, ulcerative colitis and Crohn's disease: a general population-based study. Aliment Pharmacol Ther 2006; 23 (01) 71-74
  90. De Santis A, Addolorato G, Romito A. , et al. Schizophrenic symptoms and SPECT abnormalities in a coeliac patient: regression after a gluten-free diet. J Intern Med 1997; 242 (05) 421-423
  91. John M. Celiac disease: Is it a cause of schizophrenia?. BMJ 2004; 328: 438-439
  92. Ergün C, Urhan M, Ayer A. A review on the relationship between gluten and schizophrenia: Is gluten the cause?. Nutr Neurosci 2017
  93. Buie T. The relationship of autism and gluten. Clin Ther 2013; 35 (05) 578-583
  94. Brietzke E, Cerqueira RO, Mansur RB, McIntyre RS. Gluten related illnesses and severe mental disorders: a comprehensive review. Neurosci Biobehav Rev 2017
  95. Igbinedion SO, Ansari J, Vasikaran A. , et al. Non-celiac gluten sensitivity: All wheat attack is not celiac. World J Gastroenterol 2017; 23 (40) 7201-7210
  96. Diao M, Bao J, Xu Y. [Clinical analysis of gluten-related disease]. Zhonghua Nei Ke Za Zhi 2014; 53 (11) 884-889
  97. Volta U, Bardella MT, Calabrò A, Troncone R, Corazza GR. ; Study Group for Non-Celiac Gluten Sensitivity. An Italian prospective multicenter survey on patients suspected of having non-celiac gluten sensitivity. BMC Med 2014; 12: 85
  98. Infantino M, Manfredi M, Meacci F. , et al. Diagnostic accuracy of anti-gliadin antibodies in Non Celiac Gluten Sensitivity (NCGS) patients: A dual statistical approach. Clin Chim Acta 2015; 451 (Pt B): 135-141
  99. Brusca I. Overview of biomarkers for diagnosis and monitoring of celiac disease. Adv Clin Chem 2015; 68: 1-55
  100. Infantino M, Meacci F, Grossi V, Macchia D, Manfredi M. Anti-gliadin antibodies in non-celiac gluten sensitivity. Minerva Gastroenterol Dietol 2017; 63 (01) 1-4
  101. Lundin KE. Non-celiac gluten sensitivity - why worry?. BMC Med 2014; 12: 86

How to Cite

Boarim, D. de S. F. (2022). Sensibilidade não-celíaca ao glúten. International Journal of Nutrology, 11(3), 71–79.