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Non-celiac gluten sensitivity

Non-celiac gluten sensitivity
Other namesGluten sensitivity
SpecialtyGastroenterology, internal medicine, neurology[1]
SymptomsIrritable bowel syndrome-like symptoms, fatigue, headache, fibromyalgia, atopic disorders, neurological diseases, psychiatric problems[2][3][4][5][6][7]
Usual onsetAny age[8]
Durationlifelong[9]
CausesReaction to gluten, other proteins and FODMAPS from gluten-containing cereals[3][10]
Diagnostic methodExclusion of celiac disease and wheat allergy, improvement with gluten withdrawal and worsening after gluten consumption[6][11][12]
TreatmentGluten-free diet
Frequency0.5–13%[13]

Non-celiac gluten sensitivity (NCGS) or gluten sensitivity[14] is a controversial disorder which can cause both gastrointestinal and other problems.

NCGS is included in the spectrum of gluten-related disorders.[3][4] The definition and diagnostic criteria of non-celiac gluten sensitivity were debated and established by three consensus conferences.[4][14][15][16][17] However, as of 2019, there remained much debate in the scientific community as to whether NCGS was a distinct clinical disorder.[18]

The pathogenesis of NCGS is not well understood, but the activation of the innate immune system, the direct cytotoxic effects of gluten and probably other wheat components, are implicated.[3][19][20] There is evidence that not only gliadin (the main cytotoxic antigen of gluten), but also other proteins named ATIs which are present in gluten-containing cereals (wheat, rye, barley, and their derivatives) may have a role in the development of symptoms. ATIs are potent activators of the innate immune system.[3][21] FODMAPs, especially fructans, are present in small amounts in gluten-containing grains and have been identified as a possible cause of some gastrointestinal symptoms in NCGS patients.[3][10][22][21] As of 2019, reviews have concluded that although FODMAPs may play a role in NCGS, they explain only certain gastrointestinal symptoms, such as bloating, but not the extra-digestive symptoms that people with NCGS may develop, such as neurological disorders, fibromyalgia, psychological disturbances, and dermatitis.[21][9][3]

For these reasons, NCGS is a controversial clinical condition[23] and some authors still question it.[24][25] It has been suggested that "non-celiac wheat sensitivity" is a more appropriate term, without forgetting that other gluten-containing cereals are implicated in the development of symptoms.[11][24]

NCGS is the most common syndrome of gluten-related disorders[4][26] with prevalence rates between 0.5–13% in the general population.[13] As no biomarker for diagnosing this condition is available, its diagnosis is made by exclusion of other gluten-related disorders such as celiac disease and wheat allergy.[23][27] Many people have not been diagnosed following strict criteria, and there is a "fad component" to the recent rise in popularity of the gluten-free diet, leading to debate surrounding the evidence for this condition and its relationship to celiac disease and irritable bowel syndrome.[3][5] People with NCGS are often unrecognized by specialists and lack adequate medical care and treatment.[28] They often have a long history of health complaints and unsuccessful consultations with physicians, and thus many resort to a gluten-free diet and a self-diagnosis of gluten sensitivity.[29]

  1. ^ Zis P, Hadjivassiliou M (26 February 2019). "Treatment of Neurological Manifestations of Gluten Sensitivity and Coeliac Disease". Curr Treat Options Neurol (Review). 21 (3): 10. doi:10.1007/s11940-019-0552-7. PMID 30806821. S2CID 73466457.
  2. ^ Catassi C (2015). "Gluten Sensitivity". Ann Nutr Metab (Review). 67 Suppl 2 (2): 16–26. doi:10.1159/000440990. PMID 26605537.Open access icon
  3. ^ a b c d e f g h Fasano A, Sapone A, Zevallos V, Schuppan D (May 2015). "Nonceliac gluten sensitivity". Gastroenterology (Review). 148 (6): 1195–204. doi:10.1053/j.gastro.2014.12.049. PMID 25583468. Cereals such as wheat and rye, when consumed in normal quantities, are only minor sources of FODMAPs in the daily diet. (...) Table 1. Sources of FODMAPs (...) Oligosaccharides (fructans and/or galactans). Cereals: wheat and rye when eaten in large amounts (eg, bread, pasta, couscous, crackers, biscuits)
  4. ^ a b c d Cite error: The named reference CatassiBai2013 was invoked but never defined (see the help page).
  5. ^ a b Cite error: The named reference LebwoholLudvigsson was invoked but never defined (see the help page).
  6. ^ a b Cite error: The named reference VoltaCaio2015 was invoked but never defined (see the help page).
  7. ^ Cite error: The named reference AzizHadjivassiliou2015 was invoked but never defined (see the help page).
  8. ^ Watkins RD, Zawahir S (2017). "Celiac Disease and Nonceliac Gluten Sensitivity". Pediatr Clin North Am (Review). 64 (3): 563–576. doi:10.1016/j.pcl.2017.01.013. PMID 28502438.
  9. ^ a b Cite error: The named reference VoltaDeGiorgio2019 was invoked but never defined (see the help page).
  10. ^ a b Cite error: The named reference VoltaCaioQuestions was invoked but never defined (see the help page).
  11. ^ a b Schuppan D, Pickert G, Ashfaq-Khan M, Zevallos V (Jun 2015). "Non-celiac wheat sensitivity: differential diagnosis, triggers and implications". Best Pract Res Clin Gastroenterol (Review). 29 (3): 469–76. doi:10.1016/j.bpg.2015.04.002. PMID 26060111.
  12. ^ Cite error: The named reference GreenLebwohl was invoked but never defined (see the help page).
  13. ^ a b Molina-Infante J, Santolaria S, Sanders DS, Fernández-Bañares F (May 2015). "Systematic review: noncoeliac gluten sensitivity". Aliment Pharmacol Ther (Review). 41 (9): 807–20. doi:10.1111/apt.13155. PMID 25753138. S2CID 207050854.
  14. ^ a b Ludvigsson JF, Leffler DA, Bai JC, Biagi F, Fasano A, Green PH, Hadjivassiliou M, Kaukinen K, Kelly CP, Leonard JN, Lundin KE, Murray JA, Sanders DS, Walker MM, Zingone F, Ciacci C (January 2013). "The Oslo definitions for coeliac disease and related terms". Gut (Consensus Development Conference. Research Support, N.I.H., Extramural. Research Support, Non-U.S. Gov't). 62 (1): 43–52. doi:10.1136/gutjnl-2011-301346. PMC 3440559. PMID 22345659.
  15. ^ Fasano A, Sapone A, Zevallos V, Schuppan D (May 2015). "Nonceliac gluten sensitivity". Gastroenterology (Review). 148 (6): 1195–204. doi:10.1053/j.gastro.2014.12.049. PMID 25583468. Since 2010, the definition of NCGS has been discussed at 3 consensus conferences, which led to 3 publications. 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 celiac disease and wheat allergy have been ruled out.
  16. ^ Sapone A, Bai JC, Ciacci C, Dolinsek J, Green PH, Hadjivassiliou M, Kaukinen K, Rostami K, Sanders DS, 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 (Review). 10: 13. doi:10.1186/1741-7015-10-13. PMC 3292448. PMID 22313950. Open access icon
  17. ^ Volta U, Caio G, De Giorgio R, Henriksen C, Skodje G, Lundin KE (Jun 2015). "Non-celiac gluten sensitivity: a work-in-progress entity in the spectrum of wheat-related disorders". Best Pract Res Clin Gastroenterol (Review). 29 (3): 477–91. doi:10.1016/j.bpg.2015.04.006. PMID 26060112. According to the diagnostic criteria established by two Consensus Conferences (London 2011 and Munich 2012), the current view to NCGS diagnosis is based on symptom / manifestation evaluation along with the exclusion of CD and WA [5,7].
  18. ^ Khan, Anam; Gould Suarez, Milena; Murray, Joseph (10 April 2019). "Nonceliac Gluten and Wheat Sensitivity". Clin Gastroenterol Hepatol. 2020 Aug, 18(9) (9): 1913–1922.e1. doi:10.1016/j.cgh.2019.04.009. PMID 30978535. S2CID 195661537 – via PubMed. However, there is a great deal of skepticism within the scientific community questioning the existence of NCGS as a distinct clinical disorder. There are no strict diagnostic criteria and a placebo-controlled rechallenge trial has been recommended for diagnosis
  19. ^ Cite error: The named reference ElliRoncoroni2015 was invoked but never defined (see the help page).
  20. ^ Cite error: The named reference LeonardSapone2017 was invoked but never defined (see the help page).
  21. ^ a b c Cite error: The named reference Verbeke2018 was invoked but never defined (see the help page).
  22. ^ Cite error: The named reference OntiverosHardy was invoked but never defined (see the help page).
  23. ^ a b Vriezinga SL, Schweizer JJ, Koning F, Mearin ML (Sep 2015). "Coeliac disease and gluten-related disorders in childhood". Nat Rev Gastroenterol Hepatol (Review). 12 (9): 527–36. doi:10.1038/nrgastro.2015.98. PMID 26100369. S2CID 2023530. NCGS is a clinical condition in which intestinal and extraintestinal symptoms are triggered by gluten ingestion, in the absence of coeliac disease and wheat allergy. The symptoms usually occur soon after gluten ingestion, improve or disappear within hours or a few days after gluten withdrawal, and relapse following its reintroduction. ... Unlike coeliac disease and wheat allergy, NCGS is an unclear and controversial entity.
  24. ^ a b Fasano A, Sapone A, Zevallos V, Schuppan D (May 2015). "Nonceliac gluten sensitivity". Gastroenterology (Review). 148 (6): 1195–204. doi:10.1053/j.gastro.2014.12.049. PMID 25583468. One of the most controversial and highly debated discussions concerns the role of gluten in causing NCGS. Recent reports have indicated that gluten might not be the cause of NCGS, and some investigators still question whether NCGS as a real clinical entity. (...) Cereals such as wheat and rye, when consumed in normal quantities, are only minor sources of FODMAPs in the daily diet (Table 1). Therefore, gluten-containing grains are not likely to induce IBS exclusively via FODMAPs. In contrast, there is growing evidence that other proteins that are unique to gluten-containing cereals can elicit an innate immune response that leads to NCGS, raising a nomenclature issue. For this reason, wheat sensitivity, rather than gluten sensitivity, seems to be a more appropriate term, keeping in mind that other gluten-containing grains such as barley and rye also can trigger the symptoms.
  25. ^ Makharia A, Catassi C, Makharia GK (2015). "The Overlap between Irritable Bowel Syndrome and Non-Celiac Gluten Sensitivity: A Clinical Dilemma". Nutrients. 7 (12): 10417–26. doi:10.3390/nu7125541. PMC 4690093. PMID 26690475.
  26. ^ Czaja-Bulsa G (Apr 2015). "Non coeliac gluten sensitivity – A new disease with gluten intolerance". Clin Nutr (Review). 34 (2): 189–94. doi:10.1016/j.clnu.2014.08.012. PMID 25245857. The new syndrome has been named non-celiac gluten sensitivity (NCGS) or gluten sensitivity (GS).
  27. ^ Costantino A, Aversano GM, Lasagni G, Smania V, Doneda L, Vecchi M, Roncoroni L, Pastorello EA, Elli L. Diagnostic management of patients reporting symptoms after wheat ingestion. Front Nutr. 2022 Oct 6;9:1007007. doi: 10.3389/fnut.2022.1007007. PMID: 36276818; PMCID: PMC9582535.
  28. ^ Verdu EF, Armstrong D, Murray JA (2009). "Between celiac disease and irritable bowel syndrome: the "no man's land" of gluten sensitivity". Am J Gastroenterol (Review). 104 (6): 1587–94. doi:10.1038/ajg.2009.188. PMC 3480312. PMID 19455131.
  29. ^ Cite error: The named reference mansueto-etal-2014 was invoked but never defined (see the help page).

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