NON-CELIAC GLUTEN SENSITIVITY: A TRADITIONAL REVIEW

Öz

Non-celiac gluten sensitivity (NCGS) is a disorder characterized by gastrointestinal and extra-intestinal symptoms caused by the consumption of gluten-containing foods in individuals who do not have celiac disease or wheat allergy. The limited knowledge regarding NCGS has led to various challenges in diagnosis and disease management. Due to the lack of sensitive and reproducible biomarkers for diagnosis, current evidence on NCGS prevalence is primarily based on survey studies. Although it is believed that both innate and adaptive immune systems play a role in the pathogenesis of NCGS, this remains an area of uncertainty. A gluten-free diet is recommended as the best treatment method for symptom control in NCGS. However, the gluten-free diet may lead to deficiencies in certain macro and micronutrients, and thus should be followed under the supervision of a nutritionist and clinician. With the continuously evolving body of knowledge, significant progress has been made in understanding the perspective on NCGS. The aim of this review is to provide a comprehensive overview of the etiopathogenesis, clinical features, and treatment of NCGS considering the most recent data.

Anahtar Kelimeler

• Diagnose
• Epidemiology
• Gluten-free diet
• Non-celiac gluten sensitivity

NON-ÇÖLYAK GLUTEN HASSASİYETİ: GELENEKSEL BİR DERLEME

Öz

Non-çölyak gluten hassasiyeti (NCGS), çölyak hastalığı veya buğday alerjisi olmayan bireylerde, gluten içeren besinlerin tüketimi ile gastrointestinal ve ekstraintestinal semptomlara neden olan bir bozukluktur. NCGS’ye ilişkin bilgilerin oldukça sınırlı olması, tanı koymada ve hastalık yönetiminde çeşitli zorluklara neden olmaktadır. Tanı için duyarlı ve tekrarlanabilir biyobelirteçlerin eksikliği nedeni ile NCGS prevalansını belirlenmeye yönelik mevcut kanıtlar anket çalışmalarına dayanmaktadır. NCGS patogenezinde doğuştan gelen ve adaptif bağışıklık sisteminin etkili olduğu düşünülmekle birlikte bu durum henüz netliğe kavuşturulmamıştır. NCGS’de semptomların kontrolü için en iyi tedavi yöntemi olarak glutensiz diyet önerilmektedir. Glutensiz diyet, bazı makro ve mikro besin ögelerinde eksikliklere neden olabilir bu nedenle beslenme uzmanı ve klinisyen kontrolünde yürütülmelidir. Sürekli güncellenen bilgiler ile NCGS’ye ait bakış açısında ilerleme kaydedilmektedir. Bu derleme çalışmasının amacı ise güncel bilgiler ışığında NCGS’nin etiyopatolojisi, klinik özelliklerinin daha iyi anlaşılması ve tedavisine yönelik genel bir bakış açısı sunmaktır.

Anahtar Kelimeler

• Tanı
• Epidemiyoloji
• Glutensiz diyet
• Non-çölyak gluten hassasiyeti

Kaynakça

1. Abdi, F., Zuberi, S., Blom, J. J., Armstrong, D., & Pinto-Sanchez, M. I. (2023). Nutritional Considerations in Celiac Disease and Non-Celiac Gluten/Wheat Sensitivity. Nutrients, 15(6), 1475. Doi: 10.3390/nu15061475
2. Al-Toma, A., Volta, U., Auricchio, R., Castillejo, G., Sanders, D. S., Cellier, C., Mulder, C. J., & Lundin, K. E. A. (2019). European Society for the Study of Coeliac Disease (ESsCD) guideline for coeliac disease and other gluten-related disorders. United European gastroenterology journal, 7(5), 583–613. doi: 10.1177/2050640619844125
3. Amirikian, K., Sansotta, N., Guandalini, S., & Jericho, H. (2019). Effects of the Gluten-free Diet on Body Mass Indexes in Pediatric Celiac Patients. Journal of pediatric gastroenterology and nutrition, 68(3), 360–363. doi: 10.1097/MPG.0000000000002190
4. Barbaro, M.R., Cremon, C., Stanghellini, V., & Barbara, G. (2018). Recent advances in understanding non-celiac gluten sensitivity. F1000Research,7.doi:10.12688/f1000research.15849.1 Barbaro, M.R., Cremon, C., Wrona, D., Fuschi, D., Marasco, G., Stanghellini, V., & Barbara, G. (2020). Non-celiac gluten sensitivity in the context of functional gastrointestinal disorders. Nutrients, 12(12), 3735. doi: 10.3390/nu12123735
5. Bellini, M., Tonarelli, S., Nagy, A.G., Pancetti, A., Costa, F., Ricchiuti, A., ... & Rossi, A. (2020). Low FODMAP diet: evidence, doubts, and hopes. Nutrients, 12(1), 148. doi: 10.3390/nu12010148 Cabanillas, B. (2020). Gluten-related disorders: Celiac disease, wheat allergy, and nonceliac gluten sensitivity. Critical reviews in food science and nutrition, 60(15), 2606-2621. doi: 10.1080/10408398.2019.1651689
6. Cárdenas-Torres, F.I., Cabrera-Chávez, F., Figueroa-Salcido, O.G., & Ontiveros, N. (2021). Non-celiac gluten sensitivity: an update. Medicina, 57(6), 526. doi: 10.3390/medicina57060526
7. Cardo, A., Churruca, I., Lasa, A., Navarro, V., Vázquez-Polo, M., Perez-Junkera, G., & Larretxi, I. (2021). Nutritional imbalances in adult celiac patients following a gluten-free diet. Nutrients, 13(8), 2877. doi: 10.3390/nu13082877
8. Carroccio, A., D’Alcamo, A., Iacono, G., Soresi, M., Iacobucci, R., Arini, A., ... & Mansueto, P. (2017). Persistence of nonceliac wheat sensitivity, based on long-term follow-up. Gastroenterology, 153(1), 56-58. doi: 10.1053/j.gastro.2017.03.034

9. Castillo-Rodal, A.I., Furuzawa-Carballeda, J., Peláez-Luna, M., Castro-Gómez, J., López-Vidal, Y., & Uscanga, L. (2020). More fuel to the fire: some patients with non-celiac self-reported wheat sensitivity exhibit adaptive immunological responses in duodenal mucosa. BMC gastroenterology, 20, 1-13. doi: 10.1186/s12876-020-01564-w
10. Catassi, C., Elli, L., Bonaz, B., Bouma, G., Carroccio, A., Castillejo, G., ... & Fasano, A. (2015). Diagnosis of non-celiac gluten sensitivity (NCGS): the Salerno experts’ criteria. Nutrients, 7(6), 4966-4977. doi: 10.3390/nu7064966
11. Catassi, C., Verdu, E. F., Bai, J. C., & Lionetti, E. (2022). Coeliac disease. Lancet (London, England), 399(10344), 2413–2426. Doi: 10.1016/S0140-6736(22)00794-2
12. Ciccone, A., Gabrieli, D., Cardinale, R., Di Ruscio, M., Vernia, F., Stefanelli, G., Necozione, S., Melideo, D., Viscido, A., Frieri, G., & Latella, G. (2019). Metabolic Alterations in Celiac Disease Occurring after Following a Gluten-Free Diet. Digestion, 100(4), 262–268. doi: 10.1159/000495749
13. Cooper, B. T., Holmes, G. K., Ferguson, R., Thompson, R. A., Allan, R. N., & Cooke, W. T. (1980). Gluten-sensitive diarrhea without evidence of celiac disease. Gastroenterology, 79(5 Pt 1), 801–806.
14. Di Nardo, G., Villa, M.P., Conti, L., Ranucci, G., Pacchiarotti, C., Principessa, L., ... & Parisi, P. (2019). Nutritional deficiencies in children with celiac disease resulting from a gluten-free diet: a systematic review. Nutrients, 11(7), 1588. doi: 10.3390/nu11071588
15. Efthymakis, K., Clemente, E., Marchioni, M., Di Nicola, M., Neri, M., & Sallese, M. (2020). An exploratory gene expression study of the intestinal mucosa of patients with non-celiac wheat sensitivity. International Journal of Molecular Sciences, 21(6), 1969. doi: 10.3390/ijms21061969
16. Fernandes Dias, L. B. A., Kobus, R. A., & Bagolin do Nascimento, A. (2023). Effectiveness of the low-FODMAP diet in improving non-celiac gluten sensitivity: a systematic review. The British journal of nutrition, 129(12), 2067–2075. doi: 10.1017/S0007114522002884
17. Herrera, M.G., Pizzuto, M., Lonez, C., Rott, K., Hütten, A., Sewald, N., ... & Dodero, V.I. (2018). Large supramolecular structures of 33-mer gliadin peptide activate toll-like receptors in macrophages. Nanomedicine: Nanotechnology, Biology and Medicine, 14(4), 1417-1427. doi: 10.1016/j.nano.2018.04.014
18. Husby, S., Koletzko, S., Korponay-Szabó, I., Kurppa, K., Mearin, M.L., Ribes-Koninckx, C., ... & Wessels, M. (2020). European society paediatric gastroenterology, hepatology and nutrition guidelines for diagnosing coeliac disease 2020. Journal of pediatric gastroenterology and nutrition, 70(1), 141-156. doi: 10.1097/MPG.0000000000002497
19. Jivraj, A., Hutchinson, J.M., Ching, E., Marwaha, A., Verdu, E.F., Armstrong, D., & Pinto-Sanchez, M.I. (2022). Micronutrient deficiencies are frequent in adult patients with and without celiac disease on a gluten-free diet, regardless of duration and adherence to the diet. Nutrition, 103, 111809. doi: 10.1016/j.nut.2022.111809
20. Khan, A., Suarez, M.G., & Murray, J.A. (2020). Nonceliac gluten and wheat sensitivity. Clinical Gastroenterology and Hepatology, 18(9), 1913-1922. doi: 10.1016/j.cgh.2019.04.009
21. Kulich, K.R., Madisch, A., Pacini, F., Piqué, J.M., Regula, J., Van Rensburg, C.J., ... & Wiklund, I.K. (2008). Reliability and validity of the Gastrointestinal Symptom Rating Scale (GSRS) and Quality of Life in Reflux and Dyspepsia (QOLRAD) questionnaire in dyspepsia: a six-country study. Health and quality of life outcomes, 6, 1-12. doi: 10.1186/1477-7525-6-12
22. Larretxi, I., Txurruka, I., Navarro, V., Lasa, A., Bustamante, M.Á., Fernández-Gil, M.D.P., ... & Miranda, J. (2019). Micronutrient analysis of gluten-free products: Their low content is not involved in gluten-free diet imbalance in a cohort of celiac children and adolescent. Foods, 8(8), 321. doi: 10.3390/foods8080321
23. Lionetti, E., Pulvirenti, A., Vallorani, M., Catassi, G., Verma, A.K., Gatti, S., & Catassi, C. (2017). Re-challenge studies in non-celiac gluten sensitivity: a systematic review and meta-analysis. Frontiers in Physiology, 8, 621. doi: 10.3389/fphys.2017.00621
24. Mansueto, P., Di Liberto, D., Fayer, F., Soresi, M., Geraci, G., Giannone, A.G., ... & Carroccio, A. (2020). TNF-α, IL-17, and IL-22 production in the rectal mucosa of nonceliac wheat sensitivity patients: role of adaptive immunity. American Journal of Physiology-Gastrointestinal and Liver Physiology, 319(3), G281-G288. doi: 10.1152/ajpgi.00104.2020
25. Mansueto, P., Soresi, M., La Blasca, F., Fayer, F., D’Alcamo, A., & Carroccio, A. (2019). Body mass index and associated clinical variables in patients with non-celiac wheat sensitivity. Nutrients, 11(6), 1220. doi: 10.3390/nu11061220
26. Martín-Masot, R., Nestares, M.T., Diaz-Castro, J., López-Aliaga, I., Alférez, M.J.M., Moreno-Fernandez, J., & Maldonado, J. (2019). Multifactorial etiology of anemia in celiac disease and effect of gluten-free diet: A comprehensive review. Nutrients, 11(11), 2557. doi: 10.3390/nu11112557
27. Melini, V., & Melini, F. (2019). Gluten-free diet: Gaps and needs for a healthier diet. Nutrients, 11(1), 170. doi: 10.3390/nu11010170
28. Miranda, M.E., García-Valdés, L., Espigares-Rodríguez, E., Leno-Durán, E., & Requena, P. (2023). Non-celiac gluten sensitivity: Clinical presentation, etiology and differential diagnosis. Gastroenterología y Hepatología (English Edition). doi: 10.1016/j.gastre.2022.10.010
29. Motazedian, N., Sayadi, M., Mashhadiagha, A., Moosavi, S. A., Khademian, F., & Niknam, R. (2023). Metabolic Syndrome in Celiac Disease: What Does Following a One-Year Gluten-Free Diet Bring?. Middle East journal of digestive diseases, 15(3), 185–189. doi: 10.34172/mejdd.2023.342
30. Niland, B., & Cash, B.D. (2018). Health benefits and adverse effects of a gluten-free diet in non–celiac disease patients. Gastroenterology & hepatology, 14(2), 82.
31. Penagini, F., Dilillo, D., Meneghin, F., Mameli, C., Fabiano, V., & Zuccotti, G. V. (2013). Gluten-free diet in children: an approach to a nutritionally adequate and balanced diet. Nutrients, 5(11), 4553-4565. doi: 10.3390/nu5114553
32. Penny, H.A., Baggus, E.M., Rej, A., Snowden, J.A., & Sanders, D.S. (2020). Non-responsive coeliac disease: a comprehensive review from the NHS England National Centre for Refractory Coeliac Disease. Nutrients, 12(1), 216. doi: 10.3390/nu12010216
33. Pinto-Sánchez, M.I., Causada-Calo, N., Bercik, P., Ford, A.C., Murray, J.A., Armstrong, D., ... & Green, P. (2017). Safety of adding oats to a gluten-free diet for patients with celiac disease: systematic review and meta-analysis of clinical and observational studies. Gastroenterology, 153(2), 395-409. doi: 10.1053/j.gastro.2017.04.009
34. Potter, M.D., Jones, M.P., Walker, M.M., Koloski, N.A., Keely, S., Holtmann, G., … & Talley, A.C. (2020). Incidence and prevalence of self‐reported non‐coeliac wheat sensitivity and gluten avoidance in Australia. Medical Journal of Australia, 212(3), 126-131. doi: 10.5694/mja2.50458
35. Presutti, R.J., Cangemi, J.R., Cassidy, H.D., & Hill, D.A. (2007). Celiac disease. American family physician, 76(12), 1795-1802.
36. Rinninella, E., Cintoni, M., Mele, M.C., & Gasbarrini, A. (2019). Irritable bowel syndrome (IBS) and non-celiac gluten sensitivity (NCGS): where is the culprit hiding? Nutritional tips for gastroenterologists. Nutrients, 11(10), 2499. doi: 10.3390/nu11102499
37. Roszkowska, A., Pawlicka, M., Mroczek, A., Bałabuszek, K., & Nieradko-Iwanicka, B. (2019). Non-celiac gluten sensitivity: a review. Medicina, 55(6), 222. doi: 10.3390/medicina55060222
38. Rubio-Tapia, A., Rahim, M.W., See, J.A., Lahr, B.D., Wu, T.T., & Murray, J.A. (2010). Mucosal recovery and mortality in adults with celiac disease after treatment with a gluten-free diet. Official journal of the American College of Gastroenterology| ACG, 105(6), 1412-1420. doi: 10.1038/ajg.2010.10
39. Sapone, A., Bai, J. C., Ciacci, C., Dolinsek, J., Green, P. H., Hadjivassiliou, M., Kaukinen, K., Rostami, K., Sanders, D. S., Schumann, M., Ullrich, R., Villalta, D., Volta, U., Catassi, C., & Fasano, A. (2012). Spectrum of gluten-related disorders: consensus on new nomenclature and classification. BMC medicine, 10, 13. doi: 10.1186/1741-7015-10-13
40. Schuppan, D., & Zevallos, V. (2015). Wheat amylase trypsin inhibitors as nutritional activators of innate immunity. Digestive Diseases, 33(2), 260-263. doi: 10.1159/000371476
41. Serena, G., D'Avino, P., & Fasano, A. (2020). Celiac disease and non-celiac wheat sensitivity: state of art of non-dietary therapies. Frontiers in nutrition, 7, 152. doi: 10.3389/fnut.2020.00152
42. Shahbazkhani, B., Fanaeian, M.M., Farahvash, M.J., Aletaha, N., Alborzi, F., Elli, L., ... & Rostami-Nejad, M. (2020). Prevalence of non-celiac gluten sensitivity in patients with refractory functional dyspepsia: a randomized double-blind placebo controlled trial. Scientific Reports, 10(1), 2401. doi: 10.1038/s41598-020-59532-z
43. Skodje, G. I., Sarna, V. K., Minelle, I. H., Rolfsen, K. L., Muir, J. G., Gibson, P. R., Veierød, M. B., Henriksen, C., & Lundin, K. E. A. (2018). Fructan, Rather Than Gluten, Induces Symptoms in Patients With Self-Reported Non-Celiac Gluten Sensitivity. Gastroenterology, 154(3), 529–539.e2. doi: 10.1053/j.gastro.2017.10.040
44. Sümer, S.A.G., Harmandar, F.A., Uyar, S., & Çekin, A.H. (2015). Non-Çölyak gluten duyarlılığı. Güncel Gastroenteroloji, 19(2), 91-97.
45. Sürmeli, N., & Karabudak, E. (2019). Çölyak olmayan gluten duyarlılığı. Beslenme ve Diyet Dergisi, 47(1), 66-72. doi: 10.33076/2019.BDD.1202
46. Thompson, T., & Simpson, S. (2015). A comparison of gluten levels in labeled gluten-free and certified gluten-free foods sold in the United States. European journal of clinical nutrition, 69(2), 143-146. doi: 10.1038/ejcn.2014.211
47. Uhde, M., Ajamian, M., Caio, G., De Giorgio, R., Indart, A., Green, P.H., ... & Alaedini, A. (2016). Intestinal cell damage and systemic immune activation in individuals reporting sensitivity to wheat in the absence of coeliac disease. Gut, 65(12), 1930-1937. doi: 10.1136/gutjnl-2016-312471
48. Uhde, M., Caio, G., De Giorgio, R., Green, P.H., Volta, U., & Alaedini, A. (2020). Subclass profile of IgG antibody response to gluten differentiates nonceliac gluten sensitivity from celiac disease. Gastroenterology, 159(5), 1965-1967. doi: 10.1053/j.gastro.2020.07.032
49. Vasagar, B., Cox, J., Herion, J.T., & Ivanoff, E. (2017). World epidemiology of non-celiac gluten sensitivity. Minerva gastroenterologica e dietologica, 63(1), 5-15. doi: 10.23736/s1121-421x.16.02338-2
50. Vereczkei, Z., Dergez, T., Fodor, Z., Szakács, Z., & Bajor, J. (2023). Body Mass Index during Gluten-Free Diet in Patients with Celiac Disease. Nutrients, 15(16), 3517. Doi: 10.3390/nu15163517 Vici, G., Belli, L., Biondi, M., & Polzonetti, V. (2016). Gluten free diet and nutrient deficiencies: A review. Clinical nutrition, 35(6), 1236-1241. doi: 10.1016/j.clnu.2016.05.002
51. Wieser, H., Segura, V., Ruiz-Carnicer, Á., Sousa, C., & Comino, I. (2021). Food Safety and Cross-Contamination of Gluten-Free Products: A Narrative Review. Nutrients, 13(7), 2244. doi: 10.3390/nu13072244
52. Wu, J.H., Neal, B., Trevena, H., Crino, M., Stuart-Smith, W., Faulkner-Hogg, K., ... & Dunford, E. (2015). Are gluten-free foods healthier than non-gluten-free foods? An evaluation of supermarket products in Australia. British Journal of nutrition, 114(3), 448-454. doi: 10.1017/S0007114515002056
53. Zevallos, V.F., Raker, V., Tenzer, S., Jimenez-Calvente, C., Ashfaq-Khan, M., Rüssel, N., ... & Schuppan, D. (2017). Nutritional wheat amylase-trypsin inhibitors promote intestinal inflammation via activation of myeloid cells. Gastroenterology, 152(5), 1100-1113. doi: 10.1053/j.gastro.2016.12.006