Cereals & Grains Association
Log In

02 Features
Cereal Foods World, Vol. 63, No. 5
DOI: https://doi.org/10.1094/CFW-63-5-0184
Print To PDF
Gluten Reduction Strategies for Wheat and Barley
Crispin A. Howitt,1 Philip J. Larkin,1 and Michelle L. Colgrave2

1 CSIRO Agriculture, GPO Box 1700, Canberra, ACT 2601, Australia.
2 CSIRO Agriculture, 306 Carmody Rd, St. Lucia, QLD 4067, Australia.


Gluten is a complex mixture of proteins found in wheat (gliadin and glutenins), barley (hordeins), and rye (secalins). For people with celiac disease and the less well-understood non-celiac gluten sensitivity, gluten proteins in cereals are a serious health challenge. In addition, many individuals choose to avoid gluten. In Western societies about 1% of the population is affected by celiac disease, and emerging evidence suggests that the rates may be higher than first thought in other parts of the world. Untreated celiac disease can cause a range of symptoms, including painful intestinal malignancy and greatly damaged mucosal villi, which results in poor absorption of nutrients. People with celiac disease also frequently suffer from low bone density. A less well-understood condition termed non-celiac gluten sensitivity is estimated to affect 5–10% of the population. Currently the only treatment for both is lifelong exclusion of gluten from the diet, and these diets can be low in fiber and high in fat and sugar. In an attempt to provide alternative, higher fiber dietary options research groups have been working to produce wheat and barley varieties that are safe for people who must avoid gluten in their diets. In this article we outline the progress of these efforts.

Trying to reach content?

View Full Article

if you don't have access, become a member


  1. Allred, L. K., Lesko, K., McKiernan, D., Kupper, C., and Guandalini, S. The celiac patient antibody response to conventional and gluten-removed beer. J. AOAC Int. 100:485, 2017.
  2. Aziz, I., and Hadjivassiliou, M. Coeliac disease: Noncoeliac gluten sensitivity—Food for thought. Nat. Rev. Gastroenterol. Hepatol. 11:398, 2014.
  3. Becker, D., Folck, A., Knies, P., Lörz, H., and Weiser, H. Silencing the α-gliadins in hexaploid bread wheat. Page 86 in: Gluten Proteins. G. L. Lookhart and P. K. W. Ng, eds. AACC International, St. Paul, MN, 2006.
  4. Becker, D., Wieser, H., Koehler, P., Folck, A., Mühling, K. H., and Zörb, C. Protein composition and techno-functional properties of transgenic wheat with reduced α-gliadin content obtained by RNA interference. J. Appl. Bot. Food Qual. 85:23, 2012.
  5. Biesiekierski, J. R., Newnham, E. D., Irving, P. M., Barrett, J. S., Haines, M., Doecke, J. D., Shepherd, S. J., Muir, J. G., and Gibson, P. R. Gluten causes gastrointestinal symptoms in subjects without celiac disease: A double-blind randomized placebo-controlled trial. Am. J. Gastroenterol. 106:508, 2011.
  6. Biesiekierski, J. R., Peters, S. L., Newnham, E. D., Rosella, O., Muir, J. G., and Gibson, P. R. No effects of gluten in patients with self-reported non-celiac gluten sensitivity after dietary reduction of fermentable, poorly absorbed, short-chain carbohydrates. Gastroenterology 145:320, 2013.
  7. Brennan, C. S., Smith, D. B., Harris, N., and Shewry, P. R. The production and characterisation of Hor 3 null lines of barley provides new information on the relationship of D hordein to malting performance. J. Cereal Sci. 28:291, 1998.
  8. Ciclitira, P. J., Hunter, J. O., and Lennox, E. S. Clinical-testing in celiac patients of bread made from wheats deficient in some α-gliadins. Clin. Sci. 59:25, 1980.
  9. Ciclitira, P. J., Hunter, J. O., and Lennox, E. S. Clinical testing of bread made from nullisomic 6A wheats in celiac patients. Lancet 316:234, 1980.
  10. Codex Alimentarius Commission. Standard for foods for special dietary use for persons intolerant to gluten. Standard 118-1979. In: Codex Alimentarius International Food Standards. Available online at www.fao.org/fao-who-codexalimentarius/sh-proxy/en/?lnk=1&url=https%253A%252F%252Fworkspace.fao.org%252Fsites%252
    Fcodex%252FStandards%252FCODEX%2BSTAN%2B118-1979%252FCXS_118e_2015.pdf. FAO/WHO, Rome, 2015.
  11. Colgrave, M. L., Byrne, K., and Howitt, C. A. Liquid chromatography-mass spectrometry analysis reveals hydrolyzed gluten in beers crafted to remove gluten. J. Agric. Food Chem. 65:9715, 2017.
  12. Di Sabatino, A., Volta, U., Salvatore, C., Biancheri, P., Caio, G., De Giorgio, R., Di Stefano, M., and Corazza, G. R. Small amounts of gluten in subjects with suspected nonceliac gluten sensitivity: A randomized, double-blind, placebo-controlled, cross-over trial. Clin. Gastroenterol. Hepatol. 13:1604, 2015.
  13. Doll, H. Inheritance of the high-lysine character of a barley mutant. Hereditas 74:293, 1973.
  14. Doll, H. Barley seed proteins and possibilities for their improvement. Page 207 in: Seed Proteins: Biochemistry, Genetics, and Nutritive Value. W. Gottschalk and H. P. Mullen, eds. Martinus Nishoff, The Hauge, 1983.
  15. Fasano, A., Sapone, A., Zevallos, V., and Schuppan, D. Non-celiac gluten sensitivity. Gastroenterology 148:1195, 2015.
  16. Fry, L., Madden, A. M., and Fallaize, R. An investigation into the nutritional composition and cost of gluten-free versus regular food products in the UK. J. Hum. Nut. Diet. 38:108, 2017.
  17. Gil-Humanes, J., Piston, F., Altamirano-Fortoul, R., Real, A., Comino, I., Sousa, C., Rosell, C. M., and Barro, F. Reduced-gliadin wheat bread: An alternative to the gluten-free diet for consumers suffering gluten-related pathologies. PLoS One. DOI: https://doi.org/10.1371/journal.pone.0090898. 2014.
  18. Gil-Humanes, J., Piston, F., Barro, F., and Rosell, C. M. The shutdown of celiac disease-related gliadin epitopes in bread wheat by RNAi provides flours with increased stability and better tolerance to over-mixing. PLoS One. DOI: https://doi.org/10.1371/journal.pone.0091931. 2014.
  19. Gil-Humanes, J., Piston, F., Hernando, A., Alvarez, J. C., Shewry, P. R., and Barro, F. Silencing of γ-gliadins by RNA interference (RNAi) in bread wheat. J. Cereal Sci. 48:565, 2008.
  20. Gil-Humanes, J., Piston, F., Shewry, P. R., Tosi, P., and Barro, F. Suppression of gliadins results in altered protein body morphology in wheat. J. Exp. Bot. 62:4203, 2011.
  21. Gil-Humanes, J., Pistón, F., Tollefsen, S., Sollid, L. M., and Barro, F. Effective shutdown in the expression of celiac disease-related wheat gliadin T-cell epitopes by RNA interference. Proc. Natl. Acad. Sci. U.S.A. 107:17023, 2010.
  22. Golley, S., Corsini, N., Topping, D., Morell, M., and Mohr, P. Motivations for avoiding wheat consumption in Australia: Results from a population survey. Public Health Nutr. 18:490, 2015.
  23. Green, P. H. R., Lebwohl, B., and Greywoode, R. Celiac disease. J. Allergy Clin. Immunol. 135:1099, 2015.
  24. Howitt, C. A., Bowerman, A. F., Newberry, M., Bekes, F., Larroque, O., and Morell, M. K. Suppression of gliadins by RNAi alters grain protein composition and dough functionality. Page 26 in: Cereals 2008: Proceedings of the 58th Australian Cereal Chemistry Conference. J. F. Panozzo and C. K. Black, eds. AACC International, DownUnder Section, St. Paul, MN, 2009.
  25. Junker, Y., Zeissig, S., Kim, S.-J., Barisani, D., Wieser, H., et al. Wheat amylase trypsin inhibitors drive intestinal inflammation via activation of toll-like receptor 4. J. Exp. Med. 209:2395, 2012.
  26. Kasarda, D. D., Bernardin, J. E., and Qualset, C. O. Relationship of gliadin protein components to chromosomes in hexaploid wheats (Triticum aestivum L.). Proc. Natl. Acad. Sci. U.S.A. 73:3646, 1976.
  27. Kreis, M., Shewry, P. R., Forde, B. G., Rahman, S., and Miflin, B. J. Molecular analysis of a mutation conferring the high-lysine phenotype on the grain of barley (Hordeum vulgare). Cell 34:161, 1983.
  28. Markets and Markets. Gluten-free products market by type, sales channel, and geography: Global trends and forecasts to 2019. www.marketsandmarkets.com, 2014.
  29. Mohes, C. P., Austhill, W. J., Loeffler, D., and Mullenberg, J. Reduced gluten grains and compositions thereof. Patent WO 2016196489 A1, 2018.
  30. Pistón, F., Gil-Humanes, J., Rodríguez-Quijano, M., and Barro, F. Down-regulating γ-gliadins in bread wheat leads to non-specific increases in other gluten proteins and has no major effect on dough gluten strength. PLoS One. DOI: 10.1371/journal.pone.0024754. 2011.
  31. Sanchez-Leon, S., Gil-Humanes, J., Ozuna, C. V., Gimenez, M. J., Sousa, C., Voytas, D. F., and Barro, F. Low-gluten, non-transgenic wheat engineered with CRISPR/Cas9. Plant Biotechnol. J. 16:902, 2017.
  32. Shewry, P. R. Wheat. J. Exp. Bot. 60:1537, 2009.
  33. Shewry, P. R., Bunce, N. A., Kreis, M., and Forde, B. G. Polymorphism at the Hor 1 locus of barley (Hordeum vulgare L.). Biochem. Genet. 23:391, 1985.
  34. Sollid, L. M., Qiao, S.-W., Anderson, R. P., Gianfrani, C., and Koning, F. Nomenclature and listing of celiac disease relevant gluten T-cell epitopes restricted by HLA-DQ molecules. Immunogenetics 64:455, 2012.
  35. Tanner, G. J., Blundell, M. J., Colgrave, M. L., and Howitt, C. A. Creation of the first ultra-low gluten barley (Hordeum vulgare L.) for coeliac and gluten-intolerant populations. Plant Biotechnol. J. 14:1139, 2016.
  36. Technavio. Global gluten-free beer market 2018–2022. www.technavio.com, 2018.
  37. Tye-Din, J. A., Stewart, J. A., Dromey, J. A., Beissbarth, T., van Heel, D. A., et al. Comprehensive, quantitative mapping of T cell epitopes in gluten in celiac disease. Sci. Transl. Med. 2:41, 2010.
  38. Uhde, M., Ajamian, M., Caio, G., De Giorgio, R., Indart, A., Green, P. H., Verna, E. C., Volta, U., and Alaedini, A. Intestinal cell damage and systemic immune activation in individuals reporting sensitivity to wheat in the absence of coeliac disease. Gut 65:1930, 2016.
  39. van den Broeck, H., Hongbing, C., Lacaze, X., Dusautoir, J. C., Gilissen, L., Smulders, M., and van der Meer, I. In search of tetraploid wheat accessions reduced in celiac disease-related gluten epitopes. Mol. Biosyst. 6:2206, 2010.
  40. van den Broeck, H. C., de Jong, H. C., Salentijn, E. M. J., Dekking, L., Bosch, D., Hamer, R. J., Gilissen, L. J. W. J., van der Meer, I. M., and Smulders, M. J. M. Presence of celiac disease epitopes in modern and old hexaploid wheat varieties: Wheat breeding may have contributed to increased prevalence of celiac disease. Theor. Appl. Genet. 121:1527, 2010.
  41. van den Broeck, H. C., van Herpen, T., Schuit, C., Salentijn, E. M. J., Dekking, L., Bosch, D., Hamer, R. J., Smulders, M. J. M., Gilissen, L., and van der Meer, I. M. Removing celiac disease-related gluten proteins from bread wheat while retaining technological properties: A study with Chinese spring deletion lines. BMC Plant Biol. 9:41, 2009.
  42. Wen, S. S., Wen, N. A., Pang, J. S., Langen, G., Brew-Appiah, R. A. T., et al. Structural genes of wheat and barley 5-methylcytosine DNA glycosylases and their potential applications for human health. Proc. Natl. Acad. Sci. U.S.A. 109:20543, 2012.