Fiziol. rast. genet. 2017, vol. 49, no. 3, 187-210, doi: https://doi.org/10.15407/frg2017.03.187

IS WHEAT INDEED A DESTRUCTIVE FOOD PRODUCT?

Rybalka A.I.

  • Plant Breeding and Genetics Institute—National Center of Seed and Cultivars Investigation, National Academy of Agrarian Sciences of Ukraine 3 Ovidiopolska Road, Odesa, 65036, Ukraine
  • Institute of Plant Physiology and Genetics, National Academy of Sciences of Ukraine 31/17 Vasylkivska St., Kyiv, 03022, Ukraine

The article presents a review of the main pathologies of human body such as celiac disease, wheat allergy, nonceliac wheat sensitivity, fructose malabsorption and urritable bowel syndrome, tightly related to particular compounds of wheat grain and wheat food products. The attention is predominantly focused on wheat gluten proteins the role of those in the human diet has recently been seriously scrutinized. Reactivity variation among different wheat species and genotypes, modern wheat processing and its impact on wheat sensitivity were also displayed. Causation in the increase in wheat sensitivity over the last five decades has not proven, however, modern wheat processing may be involved into exposure to human body of the immunoreactive and toxic wheat grain compounds.

Keywords: wheat, gluten, toxic peptides, immunoreactivity, celiac disease, fructose malabsorption, NCWS, IBS

Fiziol. rast. genet.
2017, vol. 49, no. 3, 187-210

Full text and supplemented materials

Free full text: PDF  

References

1. Altenbach, S., Tanaka, C. & Allen, P. (2014). Quantitative proteomic analysis of wheat grain proteins reveals differential effects of silencing of omega-5 gliadin genes in transgenic lines. J. Cereal Sci., 59, pp. 118-125. https://doi.org/10.1016/j.jcs.2013.11.008

2. Arendt, E., Ryan, L. & Dal Bello, F. (2007). Impact of sourdough on the texture of bread. Food Microbiology, 24, pp.165-174. https://doi.org/10.1016/j.fm.2006.07.011

3. Arentz-Hansen, H., Korner, R., Molberg, O., Quarsten, H., Vader, W., Kooy, Y.M., Lundin, K.E., Koning, F., Roepstoff, P., Sollid, L.M. & McAdam, S.N. (2000). The intestinal T-cell response to a-gliadin in adult celiac disease is focused on a single deamidated glutamine targeted by tissue transglutaminase. Journal of Experimental Medicine, 191, pp. 603-612. https://doi.org/10.1084/jem.191.4.603

4. Arenz-Hansen, H., McAdam, S., Molberg, O., Fleckenstein, B., Lundin, K.E., Jorgensen, T.J., Jung, G., Roepstorff, P. & Solidd, L.M. (2002). Celiac lesion T-cells recognize epitopes that cluster in regions of gliadins rich in propline residues. Gastroenterology, 123, pp. 803-809. https://doi.org/10.1053/gast.2002.35381

5. Atchison, J., Head, L. & Gates, A. (2010).Wheat as food, wheat as industrial substance; comparative geographies of transformation and mobility. Geoforum, 41, pp. 236-246. https://doi.org/10.1016/j.geoforum.2009.09.006

6. Auricchio, S., De Ritis, G., De Vincenzi, M., Occorsio, P. & Silano, V. (1982). Effects of gliadin-derived peptides from bread and durum wheats on small intestine cultures from rat and coeliac children. Pediatric Research, 16, pp. 1004-1010. https://doi.org/10.1203/00006450-198212000-00006

7. Battias, F., Courcoux, P. & Popineau, Y. (2005). Food allergy to wheat: differences in immunoglobulin E-binding proteins as a function of age or symptoms. J. Cereal Sci., 42, pp. 109-117. https://doi.org/10.1016/j.jcs.2005.01.004

8. Bigiarini, L., Pieri, N., Grilli, I., Galleschi, L., Capocchi, A. & Fontanini, D. (1995). Hydrolysis of gliadin during germination of wheat seeds. Journal of Plant Physiology, 147, pp. 161-167. https://doi.org/10.1016/S0176-1617(11)81501-4

9. Bottari, A., Capocchi, A., Fontanini, D. & Galleschi, L. (1996) Major proteinase hydrolysing gliadin during wheat germination. Phytochemistry, 43, pp. 39-44. https://doi.org/10.1016/0031-9422(96)00193-8

10. Bounaix, M-S., Gabriel, V., Morel, S., Robert, H., Rabier, P., Remaud-Simeon, M., Gabriel, B. & Fontagne-Faucher, C. (2009). Biodiversity of exopolysaccharides produced from sucrose by sourdough lactic acid bacteria. Journal of Agricultural Food Chemistry, 57, pp. 10889-10897. https://doi.org/10.1021/jf902068t

11. Brandolini, A., Hidalgo, A., , L. & Erba, D. (2011). Impact of genetic and environmental factors on einkorn wheat (Triticum monococcum L. subsp. monococcum) polysaccharides. J. Cereal Sci., 53, pp. 65-72. https://doi.org/10.1016/j.jcs.2010.09.008

12. Braun, H., Atlin, G. & Payne, P. (Eds). (2010). Multi-location testing as a tool to identify plant response to global climate change. Climate change and crop production. London: CAB International, pp. 115-138. https://doi.org/10.1079/9781845936334.0115

13. Buonocore, V., Petrucci, T. & Silano, V. (1977).Wheat protein inhibitors of alpha-amylase. Phytochemistry, 16, pp. 811-820. https://doi.org/10.1016/S0031-9422(00)86672-8

14. Capocchi, A., Muccilli, V., Cunsolo, V., Saletti, R., Foti, S. & Fontanini, D. (2013). A heterotetrameric alpha-amylase inhibitor from emmer (Triticum dicoccon Schrank) seeds. Phytochemistry, 88, pp. 6-14. https://doi.org/10.1016/j.phytochem.2012.12.010

15. Carroccio, A., Di, Prima L., Noto, D., Fayer, F., Ambrosiano, G., Villanacci, V., Lammers, K., Lafiandra, D., De Ambrogio, E., Di Fede, G., Lacono, G. & Pogna, N. (2011). Searching for wheat plants with low toxicity in celiac disease: between direct toxicity and immunologic activation. Dig. Liver. Dis., 43, pp. 34-39. https://doi.org/10.1016/j.dld.2010.05.005

16. Carroccio A., Mansueto P. & Iacono G. (2012). Non-celiac wheat sensitivity diagnosed by double-blind placebo-controlled challenge: exploring a new clinical entity. Amer. J. Gastroenterol., 107, pp. 1898-1906. https://doi.org/10.1038/ajg.2012.236

17. Catassi, C., Bai, J., Bonaz, B., Bouma, G., Calabro, A., Carroccio, A., Castillejo, G., Carolina, C., Cristofori, F., Dolinsek, J., Francavilla, R., Elli, L., Green, P., Holtmeier, W., Koehler, P., Koletzko, S., Meinhold, C., Sanders, D., Schumann, M., Schuppan, D., Ullrich, R., Vecsei, A., Volta, U., Zevallos, V., Sapone, A. & Fasano, A. (2013). Non-celiac gluten sensitivity: the new frontier of gluten related disorders. Nutrients, 5, pp. 3839-3853. https://doi.org/10.3390/nu5103839

18. Choudhury, A., Maeda, K., Murayama, R. & DiMagno, E. Character of a wheat amylase inhibitor preparation and effects on fasting human pancreaticobiliary secretions and hormones. Gastroenterology, 111, pp. 1313-1320. https://doi.org/10.1053/gast.1996.v111.pm8898646

19. Cinova, J., Palova-Jelinkova, L. & Smythies, L. (2007). Gliadin peptides activate blood monocytes from patient with celiac disease. J. Clin. Immunol., 27, pp. 201-209. https://doi.org/10.1007/s10875-006-9061-z

20. Constantin, C., Touraev, A., Heberle-Bors E. & Quirce, S. (2009). Detection of antigens reactive to IgE and IgA during wheat ssed maturation and in different wheat cultivars. International Archives of Allergy and Immunology, 149, 181-187. https://doi.org/10.1159/000199713

21. Davis, W. (2011). Wheat belly: lose the wheat, lose the weight, and find your path back to health. Emmaus, Pa: Rodale Press, 290 p.

22. Dawson, J., Kutka, F., Russell, J. & Zwinger, S. (2013). The «ancient» grains emmer, einkorn, and spelt: what we know and what we need to find out. Corvallis, USA: eOrganic.

23. Day, L., Augustin, M., Batey, I. & Wrigley, C. (2006). Wheat-gluten uses and industry needs. Trends in Food Science and Technology, 17, pp. 82-90. https://doi.org/10.1016/j.tifs.2005.10.003

24. De Angelis, M., Cassone, A., Rizzello, C., Garliardi, F., Minervini, F., Calasso, M., Di Cagno, R., Francayilla, R. & Gobetti, M. (2010). Mechanism of degradation of immunogenic gluten epitopes from Triticum turgidum L. var. durum by sourdough lactobacilli and fungal proteases. Applied and Environmental Microbiology, 76, pp. 508-518. https://doi.org/10.1128/AEM.01630-09

25. De Gara, L., de Pinto, M., Moliterni, V. & D'Egidio, M. (2003). Redox regulation and storage processes during maturation in kernels of Triticum durum. Journal of Experimental Botany, 54, pp. 249-258. https://doi.org/10.1093/jxb/erg021

26. Denery-Papini, S., Laurierre, M., Branlard, G., Morisset, M., Pesquet, C., Choudat, D., Merlino, M., Pineau, F., Popineau, Y., Boulenc, E., Bouchez-Mahiout, I., Bodinier, M. & Moneret-Vautrin, D.A. (2007). Influence of the allelic variants encoded at the Gli-B1 locus, responsible for a major allergen of wheat, on IgE reactivity for patients suffering from food allergy to wheat. Journal of Agricultural Food Chemistry, 55, pp. 799-805. https://doi.org/10.1021/jf062749k

27. Di Cagno, R., Barbato, M., Di Camillo, C., Rizello, C.G., De Angelis, M., Giuliani, G., De Vincenzi, M., Gobetti, M. & Cucchiara, S. (2010). Gluten-free sourdough wheat baked goods appear safe for young celiac patients: a pilot study. J. Pediatr. Gastroenterol. Nutr., 51, pp. 777-783. https://doi.org/10.1097/MPG.0b013e3181f22ba4

28. Di Cagno R., De Angelis M., Alfonsi G., De Vincenzi, M., Silano, M., Vincentini, O. & Gobbetti, M. Pasta made from durum wheat semolina fermented with selected lactobacilli as a tool for a potential decrease of the gluten intolerance. Journal of Agricultural Food Chemistry, 53, pp. 4393-4402. https://doi.org/10.1021/jf048341+

29. Digiacomo, D., Tennyson, C., Green, P. & Demmer, R. (2013). Prevalence of gluten-free diet adherence among individuals without celiac disease in the USA: result from the Continuous National Health and Nutrition Examination Survey 2009/2010. Scandinavian Journal of Gastroenterology, 48, pp. 921-925. https://doi.org/10.3109/00365521.2013.809598

30. Escriva, C. & Martinez-Anaya, M. (2000). Influence of enzymes on the evolution of fructosans in sourdough wheat processes. European Food Research and Technology, 210, pp. 286-292. https://doi.org/10.1007/s002179900096

31. Fedewa, A. & Rao, S.S. (2014). Dietary fructose intolerance, fructan intolerance and FODMAPs. Curr. Gastroenterol. Rep., 16, p. 370. https://doi.org/10.1007/s11894-013-0370-0

32. Fedewa, A. & Rao, S.S. (2014). Dietary fructose intolerance, fructan intolerance and FODMAPs. Curr. Gastroenterol. Rep., 16, p. 370. https://doi.org/10.1007/s11894-013-0370-0

33. Freitag, T., Loponen, J., Messing, M., Zevallos, V., Andersson, L.C., Sontaq-Strohm, T., Saayalainen, P., Schuppan, D., Saloyaara, H. & Meri, S. (2014). Testing safety of germinated rye sourdough in a celiac disease model based on the adoptive transfer of prolamin-primed memory T-cells into lymphopenic mice. AJP Gastrointestinal and Liver Physiology, 306, pp. 526-534 https://doi.org/10.1152/ajpgi.00136.2013

34. Frisoni M., Corazza G., Lafiandra D. & De Ambrogio, E. (1995). Wheat deficient in gliadins: promising tool for treatment of coeliac disease. Gut, 36, pp. 375-378. https://doi.org/10.1136/gut.36.3.375

35. Gallo, G., De Angelis & M., McSweeney, P. (2005). Partial purification and characterization of an X-prolyl dipeptidyl amino peptidase from Lactobacillus sanfranciscensis CB1. Food Chemistry, 9, pp. 535-544. https://doi.org/10.1016/j.foodchem.2004.08.047

36. Ganzle, M., Loponen, J. & Gobbetti, M. (2008). Proteolysis in sourdough fermentations: mechanisms and potential for improved bread quality. Trends in Food Science & Technology, 19, pp. 513-521. https://doi.org/10.1016/j.tifs.2008.04.002

37. Gibson P., Newnham E., Barrett J. & Shepherd, S.J. (2007). Review article: fructose malabsorption and the bigger picture. Alimentary Pharmacology & Therapeutics, 25, pp. 349-363. https://doi.org/10.1111/j.1365-2036.2006.03186.x

38. Gil-Humanes J., Pistorn F., Tollefsen S., Sollid, L.M. & Barro, F. (2010). Effective shutdown in the expression of celiac disease-related wheat gliadin T-cell epitopes by RNA interference. Proc. Natl. Acad. Sci. USA.,107, pp. 17023-17028. https://doi.org/10.1073/pnas.1007773107

39. Gluten-free products market worth 7,59 billion USD by 2020. http://www.marketsandmarkets.com/Market-Reports/gluten-free

40. Gobbetti, M., Giuseppe Rizzello, C., Di Cagno, R. & De Angelis, M. (2007). Sourdough lactobacilli and celiac disease. Food Microbiology, 24, pp. 187-196. https://doi.org/10.1016/j.fm.2006.07.014

41. Grabitske, H. & Slavin, J. (2009). Gastrointestinal effect of low-digestible carbohydrates. Critical revievs in food science and nutrition, 49, pp. 327-360. https://doi.org/10.1080/10408390802067126

42. Greco, L., Gobbetti, M., Auricchio, R. & Di Mase, R. (2011). Safety for patients with celiac disease of baked goods made of wheat flour hydrolyzed during food processing. Clinical gastroenterology and hepatology, 9, pp. 24-29. https://doi.org/10.1016/j.cgh.2010.09.025

43. Halmos, E., Power, V., Shepherd, S., Gipson, P. & Muir, J. (2014). A diet low in FODMAPs reduces symptoms of irritable bowel syndrome. Gastroenterology, 146, pp. 67-75. https://doi.org/10.1053/j.gastro.2013.09.046

44. Hammed, A. (2014). Hulled wheats: a review of nutritional properties and processing methods. Cereal Chemistry, 91, pp. 97-104. https://doi.org/10.1094/CCHEM-09-13-0179-RW

45. Hammerton, R. & Ho, T-H. (1986). Hormonal regulation of the development of protease and carboxypeptidase activities in barley aleurone layers. Plant Physiology, 80, pp. 692-697. https://doi.org/10.1104/pp.80.3.692

46. Hartmann, G., Koehler, P. & Wieser, H. (2006). Rapid degradation of gliadin peptides toxic for coeliac disease patients by proteases from germinating cereals. J. Cereal Sci., 44, pp. 368-371. https://doi.org/10.1016/j.jcs.2006.10.002

47. Haska, L., Nyman, M. & Andersson, R. (2008). Distribution and characterization of fructan in wheat milling fractions. J. Cereal Sci., 48, pp. 768-774. https://doi.org/10.1016/j.jcs.2008.05.002

48. Hausch, F., Shan, L., Santiago, L. & Gray, G. (2002). Intestinal digestive resistance of immunodominant gliadin peptides. AJP Gastrointestinat and Liver Physiology, 283, pp. 996-1003. https://doi.org/10.1152/ajpgi.00136.2002

49. Hendry, G. (1993). Evolutionary origins and natural functions of fructans — a climatological, biogeographic and mechanistic appraisal. New Phytologist, 123, pp. 3-14. https://doi.org/10.1111/j.1469-8137.1993.tb04525.x

50. Hischenhuber, C., Crevel, R., Jarry, B. & Maki, M. (2006). Review article: safe amounts of gluten for patients with wheat allergy or coeliac disease. Alimentary Pharmacology and Therapeutics, 23, pp. 559-575. https://doi.org/10.1111/j.1365-2036.2006.02768.x

C51. Hungin A., Chang L., Locke G., Dennis, E. & Barghout, V. (2005). Irritable bowel syndrome in the United States: prevalence, symptom patterns and impact. Alimentary Pharmacology & Therapeutics, 21, pp. 1365-1375. https://doi.org/10.1111/j.1365-2036.2005.02463.x

52. Hungin, A., Whorwell, P., Tack, J. & Mearin, F. (2003). The prevalence, patterns and impact of irritable bowel syndrome: an international survey of 40 000 subjects. Alimentary Pharmacology & Therapeutics, 17, pp. 643-650. https://doi.org/10.1046/j.1365-2036.2003.01456.x

53. Hurkman W., Tanaka C., Vensel W., Thilmony, R. & Altenbach, S. (2013). Comparative proteomic analysis of the effect of temperature and fertilizer on gliadin and glutenin accumulation in the developing endosperm and flour from Triticum aestivum L. cv. Butte 86. Proteome Science, 11:8. doi: 10.1186/1477-5956-11-8. https://doi.org/10.1186/1477-5956-11-8

54. Huynh, B.-L., Palmer, L. & Mather, D. (2008). Genotypic variation in wheat grain fructan content revealed by a simplified HPLC method. J. Cereal Sci., 48, 369-378. https://doi.org/10.1016/j.jcs.2007.10.004

55. Jackson J., Eaton W., Cascella N., Fasano, A. & Kelly, D. (2012). Neurologic and psychiatric manifestations of celiac disease and gluten sensitivity. Psychiatr Q, 83, pp. 91-102. https://doi.org/10.1007/s11126-011-9186-y

56. Junker Y., Zeissing S., Kim S-J. & Barisani, D. (2012). Wheat amylase trypsin inhibitors drive intestinal inflammation via activation of toll-like receptor 4. Journal of Experimental Medicine, 209, pp. 2395-2408. https://doi.org/10.1084/jem.20102660

57. Kanerva, P. (2011). Immunochemical analysis of prolamins in gluten-free foods (PhD Thesis). University of Helsinki, pp. 2-3. 

58. Kasarda, D., Bernardin, J. & Nimmo, C. (1976). Wheat proteins. Advances in Cereal Science and Technology. A.A.C.C. St. Paul, Minnesota, USA, pp. 158-236.

59. Klessen, B., Schwarz, S., Boehm A., Fuhrmann, H., Richter, A., Henie, T. & Krueger, M. (2007). Jerusalem artichoke and chicory inulin in bakery products affect fecal microbiota of healthy volunteers. Br. J. Nutr., 98, pp. 540-549. https://doi.org/10.1017/S0007114507730751

60. Knez, M., Abbott, C. & Stangoulis, J. (2014). Changes in the content of fructans and arabinoxylans during baking processes of leavened and unleavened breads. European Food Research and Technology, 239, pp. 803-811. https://doi.org/10.1007/s00217-014-2273-1

61. Krahl M., Muller S., Zarnkow M. & Becker, T. (2009). Arabinoxylan and fructan in the malting and brewing process. Quality Assurance and Safety of Crops & Foods banner, 1, pp. 246-255. https://doi.org/10.1111/j.1757-837X.2009.00035.x

62. Kucek, L., Veenstra, L., Amnuaycheewa, P. & Sorrells, M. (2015). A grounded guide to gluten: how modern genotypes and processing impact wheat sensitivity. Comprechensive Reviews in Food Science and Food Safety, Instut Food Technology, 14, pp. 285-302. https://doi.org/10.1111/1541-4337.12129

63. Lafiandra, D., Splendido, R., Tomassini, C. & Al, E. (Eds). (1987). Lack of expression of certain storage proteins in bread wheats: distribution and genetic analysis of null forms. R. Laszity, F. Bekes (ed). Proc. 3rd Int. Workshop on Gluten Proteins. Budapest, Hungary: World Sci. Pud. Co. Inc., pp. 71-90.

64. Lammers, K., Lu, R., Brownley, J., Lu, B., Gerard, C., Thomas, K., Rallabhandi, P., Shea-Donohue, H., Tamiz, A., Alkan, S., Netzel-Arnett, S., Antalis, T., Vogel, S.N. & Fasano, A. (2008). Gliadin induces an increase in intestinal permeability and zonulin release by binding to the chemokine receptor CXCR3. Gastroenterology, 135, pp. 194-204.e3. https://doi.org/10.1053/j.gastro.2008.03.023

65. Laurie're M., Pecquet C., Bouchez-Mahiout I., Snegaroff, J., Bayrou, O., Raison-Peyron, N. & Vigan, M. (2006). Hydrolysed wheat proteins present in cosmetics can induce immediate hypersensitivities. Contact Dermatitis, 54, pp. 283-289. https://doi.org/10.1111/j.0105-1873.2006.00830.x

66. Leduc, V., Moneret-Vautrin, D.-A., Guerin L., Mirisset, M. & Kanny, G. (2003). Anaphylaxic to wheat isolates: immunochemical study of a case proved by means of double-blind, placebo-controlled food challenge. J. Allergy Clin. Immunol., 111, pp. 897-899. https://doi.org/10.1067/mai.2003.1345

67. Leszczynska J., Lacka A., Szemraj J. & Lukamowicz, J. (2003). The effect of microwave treatment on the immunoreactivity of gliadin and wheat flour. European Food Research and Technology, 217, pp. 387-391. https://doi.org/10.1007/s00217-003-0765-5

68. Lindfors K. & Kaukinen K. (2012). Contribution of celiac disease autoantibodies to the disease process. Expert Review of Clinical Immunology, 8, pp. 151-154. https://doi.org/10.1586/eci.11.89

69. Loponen, J., Kanerva, P., Zhang, C. & Sontrag-Strohm, T. (2009). Prolamin hydrolysis and pentosan solubilization in germinated-rye sourdoughs determined by chromatographic and immunological methods .Journal of Agricultural and Food Chemistry, 57, pp. 746-753. https://doi.org/10.1021/jf803243w

70. Loponen, J., Sontag-Strohm, T., Venalainen, J. & Salovaara, H. (2007). Prolamin hydrolysis in wheat sourdoughs with differing proteolytic activities. Journal of Agricultural and Food Chemistry, 55, pp. 978-984. https://doi.org/10.1021/jf062755g

71. Ludvigsson, J., Leffler, D. & Bai, J. (2013). The Olso definition for celiac disease and related terms. Gut., 62, pp. 43-52. https://doi.org/10.1136/gutjnl-2011-301346

72. Luoto S., Jiang Z., Brinck O., Sontrag-Strohm, T., Kanerva, P., Bruins, M., Edens, L., Salovaara, H. & Loponen, J. (2012). Malt hydrolysates for gluten-free applications: autolytic and proline endopeptidase assisted removal of prolamins from wheat, barley and rye. J. Cereal Sci., 56, pp. 504-509. https://doi.org/10.1016/j.jcs.2012.06.004

73. Lupi, R., Masci, S., Rogniaux H. & Tranguet, O. (2014). Assessment of the allergenicity of soluble fractions from GM and commercial genotypes of wheats. J. Cereal Sci., 60, pp.179-186. https://doi.org/10.1016/j.jcs.2014.02.009

74. Matysiak-Budnik T., Candalh C., Cellier C., Dugave, C., Namane, A., Vidal-Martinez, T., Cerf-Bensussan, N. & Heyman, M. (2005). Limited efficiency of prolylendopeptidase in the detoxification of gliadin peptides in celiac disease. Gastroenterology, 129, pp. 786-796. https://doi.org/10.1053/j.gastro.2005.06.016

75. M'hir S., Ziadi M., Chammem N. & Hamdi M. (2012). Gluten proteolysis as alternative therapy for celiac patients: a mini-review. African Journal Biotechnology, 11, pp.7323-7330.

76. Molberg, O., Uhlen, A., Jensen, T., Flaete, N.C., Fleckenstein, B., Arentz-Hansen, H., Raki, M., Lundin, K.E. & Sollid, L.M. (2005). Mapping of gluten T-cell epitopes in the bread wheat ancestors: implications for celiac disease. Gactroenterology, 128, pp. 393-401. https://doi.org/10.1053/j.gastro.2004.11.003

77. Morita E., Matsuo H., Chinuki Y., Takahashi, H., Dahistrom, J. & Tanaka, A. (2009). Food-dependent exercise-induced anaphylaxis importance of omega-5 gliadin and HMW-glutenin as causative antigens for wheat-dependent exercise-induced anaphylaxis. Allergology International, 58, pp. 493-498. https://doi.org/10.2332/allergolint.09-RAI-0125

78. Muller, M. & Lier, D. (1994). Fermentation of fructans by epiphytic lactic acid bacteria. Journal of Applied Bacteriology, 76, pp. 406-411. https://doi.org/10.1111/j.1365-2672.1994.tb01647.x

79. Nakamura A., Tanabe S., Watanabe J. & Makino, T. (2005). Primary screening of relatively less allergenic wheat carieties. Journal of Nutritional Science and Vitaminology, 51, pp. 204-206. https://doi.org/10.3177/jnsv.51.204

80. Nilsson, U., Oste, R. & Jagerstad, M. (1987). Cereal fructans: Hydrolysis by yeast invertase, in vitro and during fermentation. J. Cereal Sci., 6, pp. 53-60. https://doi.org/10.1016/S0733-5210(87)80040-1

81. Nutritional Association of Wheat Growers. 2013, Wheat Info, Accessed 2012, March 3.

82. Pizzuti D., Buda A., D'Odorico, A. & D'lnca, R. (2006). Lack of intestinal mucosal toxicity of Triticum monococcum in celiac disease patients. Scandinavian Journal of Gastroenterology, 41, pp. 1305-1311. https://doi.org/10.1080/00365520600699983

83. Prandi, B., Faccini, A., Tedeschi, T., Galaverna, G. & Sforza, S. (2013). LC/MS analysis of proteolytic peptides in wheat extracts for determining the content of the allergen amylase/trypsin inhibitor CM3: influence of growing area and variety. Food Chemistry, 140, pp. 141-146. https://doi.org/10.1016/j.foodchem.2013.02.039

84. Praznik, W., Ciesrlik, E. & Filipiak-Florkiewicz, A. (2002). Soluble dietary fibres in Jerusalem artichoke powders: composition and application in bread. Nahrung., 46, pp.151-157. https://doi.org/10.1002/1521-3803(20020501)46:3<151::AID-FOOD151>3.0.CO;2-4

85. Quirce S., Fernarndez-Nieto M., Bartolomer B., Bombin, C., Cuevas, M. & Sastre, J. (2002). Glucoamylase: another fungal enzyme associated with baker's asthma. Ann. Allergy Asthma Immunol., 89, pp. 197-202. https://doi.org/10.1016/S1081-1206(10)61938-2

86. Rathi, P. & Zanwar, V. (2016). Non-celiac gluten sensitivity (NCGS). Journal of the Association of Physicians of India, 64, pp. 46-55.

87. Rewers, M. (2005). Epidemiology of celiac disease: what are the prevalence, incidence, and progression of celiac disease? Gastroenterology, 128, pp.47-51. https://doi.org/10.1053/j.gastro.2005.02.030

88. Rizzello, C., De Angelis, M., Di Cagno, R., Camarca, A., Silano, M., Losito, I., De Bari, M.D., Palmisano, F.,Maurano, F., Gianfani, C. & Gobetti, M. (2007). Highly efficient gluten degradation by lactobacilli and fungal proteases during food processing: new perspectives for celiac disease. Appl. Environ. Microbiol., 73, pp. 4499-4507. https://doi.org/10.1128/AEM.00260-07

89. Roberfroid, M., Gibson, G. & Hoyles, L. (2010). Prebiotic concept and health // British Journal of Nutrition, 104, pp. 61-63.

90. Rubio-Tapia A., Kyle R., Kaplan E., Johnson, D.R., Page, W., Erdtman, F., Brantner, T., Kim, W., Phelps, T., Lahr, B., Zinsmeister, A., Melton, L. & Murray, J. (2009). Increased prevalence and mortality in undiagnosed celiac disease. Gastroenterology, 137, pp. 88-93. https://doi.org/10.1053/j.gastro.2009.03.059

91. Rumessen J. & Gudmand-Hoyer E. (1998). Fructans of chicory: intestinal transport and fermentation of different chain lengths and relation to fructose and sorbitol malabsorption. American journal of clinical nutrition, 68, pp. 357-364. https://doi.org/10.1093/ajcn/68.2.357

92. Salentijn, E., Esselink, D., Goryunova, S., van der Meer, I., Gilisen, L. & Smulders, M. (2013). Quantitative and qualitative differences in celiac disease epitopes among durum wheat varieties identified through deep RNA-amplicon sequencing. BMC Genomics, 14:905. doi: 10.1186/1471-2164-14-905. https://doi.org/10.1186/1471-2164-14-905

93. Sanchez-Monge, R., Garcia-Casado, G., Malpica,, J. & Salcedo, G. (1996). Inhibitory activities against heterologous a-amylases and in vitro allergenic reactivity of Einkorn wheats. Theoretical and Applied Genetics, 93, pp. 745-750. https://doi.org/10.1007/BF00224071

94. Sandiford, C., Tatham, A., Fido, R. & Welch, J. (1997). Identification of the major water/salt insoluble wheat proteins involved in cereal hypersensitivity. Clinical & Experimental Allergy, 27, pp. 1120-1129. https://doi.org/10.1111/j.1365-2222.1997.tb01148.x

95. Sapone A., Bai J., Ciacci C., Dolinsek, J., Green, P., Hadivassiliou, M., Kaukinen, K., Rostami, K., Sanders, D., Schumann, M., Ultrich, R., Villalta, D., Volta, U., Catassi, C. & Fasano, A. (2012). Spectrum of gluten-related disorders: consensus on new nomenclature and classification. BMC Med., 10, pp.1711-1715. https://doi.org/10.1186/1741-7015-10-13

96. Schwalb, T., Wieser, H. & Koehler, P. (2012). Studies on the gluten-specific peptidase activity of germinated grains from different cereal species and cultivars. European Food Research and Technology, 235, pp. 1161-1170. https://doi.org/10.1007/s00217-012-1853-1

97. Seilmeier, W., Valdez, I., Mendez, E. & Wieiser, H. (2001). Comparative investigations of gluten proteins from different wheat species. II. Characterization of w-gliadins. European Food Research and Technology, 212, pp. 355-363. https://doi.org/10.1007/s002170000260

98. Shepherd, S. & Gibson, P. (2006). Fructose malabsorption and symptoms of irritable bowel syndrome: guideline for effective dietary management. Journal of the American Dietetic Association, 106, pp.1631-1639. https://doi.org/10.1016/j.jada.2006.07.010

99. Shepherd, S., Parker, F., Muir, J.& Gibson, P. (2008). Dietary triggers of abdominal symptoms in patients with irritable bowel syndrome: randomized placebo-controlled evidence. Clinical Gastroenterology and Hepatology, 6, pp. 765-771. https://doi.org/10.1016/j.cgh.2008.02.058

100. Spaenij-Dekking, L., Kooy-Winkelaar, Y., van Veelen, P., Drijfhout, J., Jonker, H., van Soest, L., Smulders, M., Bosch, D., Gilisen, L. & Koning. (2005). Natural variation in toxicity of wheat: potential for selection of nonotoxic varieties for celiac disease patients. Gastroenterology, 129, pp. 797-806. https://doi.org/10.1053/j.gastro.2005.06.017

101. Stenman, S., Lindfors, K., Venalainen, J., Hautala, A., Mannisto, P., Garsia-Horsman, J., Kaukovirta-Norga, A., Auriola, S., Mauriala, T., Maki, M. & Kaukinen, K. (2010). Degradation of celiac disease-inducing rye secalin by germinating cereal enzymes: diminishing toxic effects in intestinal epithelial cells. Clinical & Experimental Immunology, 161, pp. 242-249. https://doi.org/10.1111/j.1365-2249.2010.04119.x

102. Stenman, S., Venalainen, J., Lindfors, K., Auriola, S., Mauriala, T., Kaukovirta-Norja, A., Jantunen, A., Laurila, K., Qiao, S., Sollid, L., Mannistro, P., Kaukinen, K. & Maki, M. (2009). Enzymatic detoxification of gluten by germinating wheat proteases: implications for new treatment of celiac disease. Annals of Medicine, 41, pp. 390-400. https://doi.org/10.1080/07853890902878138

103. Stepniak, D., Vader, L., Kooy, Y. & van Veelen, P. (2005). T-cell recognition of HLA-DQ2-bound gluten peptides can be influenced by an N-terminal proline at p-1. Immunogenetics, 57, pp. 8-15. https://doi.org/10.1007/s00251-005-0780-8

104. Tanabe, S. (2004). IgE-binding abilities pf pentapeptides, QQPFP and PQQPF, in wheat gliadin. J. Nutr. Sci. Vitaminol., 50, pp. 367-370. https://doi.org/10.3177/jnsv.50.367

105. Tatham, A. & Shewry, P. (2008). Allergens to wheat and related cereals. Clinical & Experimental Allergy, 38, pp. 1712-1726.

106. Taylor, S. & Hefle, S. (2001). Food allergies and other food sensitivities. Sci. Status Summ. Food Technol., 55, pp. 68-83.

107. Thomas, K., Sapone, A., Fasano, A. & Vogel, S. (2006). Gliadin stimulation of murine macrophage inflammatory gene expression and intestinal permeability are MyD88-dependent: role of the innate immune response in celiac disease. Journal of Immunology, 176, pp. 2512-2521. https://doi.org/10.4049/jimmunol.176.4.2512

108. Tosi, P., Gritsch, C., He, J., Shewry, P. (2011). Distribution of gluten proteins in bread wheat (Triticum aestivum) grain. Annals of Botany, 108, pp.23-35. https://doi.org/10.1093/aob/mcr098

109. Tjon, J., Bergen, J. & Koning, F. (2010). Celiac disease: how complicated can it get? Immunogenetics, 62, pp. 641-651. https://doi.org/10.1007/s00251-010-0465-9

110. Tripathi A., Lammers K. & Goldblum S. (2009). Identification of human zonulin, a physiological modulator of tight junctions, as prehaptoglobin-2. Proceedings of the National Academy of Sciences USA, 106, pp. 16799-16804. https://doi.org/10.1073/pnas.0906773106

111. Tye-Din, J., Stewart, J., Dromey, J.,Beissbarth, T., van Heel, D., Tatham, A., Henderson, K., Mannering, S., Gianfrani, C., Jewell, D., Hill, A., McCluskev, J., Rossiohn, J. & Anderson, R. (2010). Comprehensive, quantitative mapping of T-cell epitopes in gluten in celiac disease. Science Translational Medicine, 2, pp.1-14. https://doi.org/10.1126/scitranslmed.3001012

112. van den Broeck H., de Jong H., Salentijn E., Dekking, L., Bosch, D., Hamer, R., Gilissen, L., van der Meer, I. & Smulders, M. (2010). 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, pp. 1527-1539. https://doi.org/10.1007/s00122-010-1408-4

113. van den Broeck, H., van Herpen, T., Schuit, C., Salentijn, M., Dekking, L., Bosch, D., Hamer, R., Smulders,M., Gilissen, L. & van der Meer, I. (2009). et al. Removing celiac disease-related gluten proteins from bread wheat while retaining technological properties: a study with Chinese Spring deletion lines. BMC Plant Biology, 9:41.doi:10.1186/1471-2229-9-41. https://doi.org/10.1186/1471-2229-9-41

114. van Herpen, T., Goryunova, S., van der Schoot, J., Mitreva, M., Salentijn, E., Vorst, O., Schenk, M., van Veelen, P., Koning, F., van, Soest L., Vosman, B., Bosch, D., Hamer, R., Gilisen, L. & Smulders, M. (2006). Alphagliadin genes from the A, B, and D genomes of wheat contain different sets of celiac disease epitopes. BMC Genomics, doi: 10.1186/1471-2164-7-1. https://doi.org/10.1186/1471-2164-7-1

115. Vincentini, O., Borrelli, O., Silano, M., Gazza, L., Pogna, N., Luchetti, R., De Vincenzi, M. (2009). T-cell response to different cultivars of farro wheat, Triticum turgidum ssp. dicoccum, in celiac disease patients. Clin. Nutr., 28, pp. 272-277. https://doi.org/10.1016/j.clnu.2009.03.013

116. Vincentini, O., Maialetti, F., Gazza, L. Silano, M., De Vincenzi, M. & Pogna, N. (2007). Environmental factors of celiac disease: cytotoxicity of hulled wheat species Triticum monococcum, T. turgidum ssp. dicoccum and T. aestivum ssp. Spelta. Journal of Gastroenterology and Hepatology, 22, pp. 1816-1822. https://doi.org/10.1111/j.1440-1746.2006.04680.x

117. Volta, U., Tovoli, F., Cicola, R., Parisi, C, Fabbri, A., Piscaglia, M., Fiorini, E. & Caio, G. (2012). Serological tests in gluten sensitivity (nonceliac gluten intolerance). Journal of Clinical Gastroenterology, 46, pp. 680-685. https://doi.org/10.1097/MCG.0b013e3182372541

118. Waga, J. & Skoczowski, A. (2014). Development and characteristics of w-gliadin-free wheat genotypes. Euphytica, 195, pp. 105-116. https://doi.org/10.1007/s10681-013-0984-1

119. Walusiak, J., Hanke, W., Gorski, P. & Palczynski, C. (2004). Respiratory allergy in apprentice bakers: do occupational allergies follow the allergic march?. Allergy., 59, pp. 442-450. https://doi.org/10.1111/j.1398-9995.2003.00418.x

120. Wang, J-R., Yan, Z-H. & Wei, Y-M. (2006). Molecular characterization of dimeric alpha-amylase inhibitor genes in wheat and development of genome allele-specific primers for the genes located on chromosome 3BS and 3DS. J. Cereal Sci., 43, pp. 360-368. https://doi.org/10.1016/j.jcs.2005.12.005

121. Wieser, H., Seilmeier, W. & Belitz, H. (1994). Quantitative determination of gliadin subgroups from different wheat cultivars. J. Cereal Sci., 19, pp. 149-155. https://doi.org/10.1006/jcrs.1994.1020

122. Wieser, H., Vermeulen, N., Gaertner, F. & Vogel, R. (2008). Effect of different Lactobacillus and Enterococcus strains and chemical acidification regarding degradation of gluten proteins during sourdough fermentation. Eur. Food Res. Technol., 226, pp. 1495-1502. https://doi.org/10.1007/s00217-007-0681-1

123. Zoccatelli, G., Sega, M., Bolla, M., Cecconi, D., Vaccino, P., Rizzi, C., Chignola, R. & Brandolini, A. (2012). Expression of a-amylase inhibitors in diploid Triticum species. Food Chem., 135, pp. 2643-2649. https://doi.org/10.1016/j.foodchem.2012.06.123