Recent Advances in Biotechnological Methods for Wheat Gluten Immunotoxicity Abolishment – a Review
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Food Institute, Kaunas University of Technology, Radvilenu road 19C-413, Kaunas, Lithuania
Food Technology Department, Klaipeda State University of Applied Sciences, Bijunu street 10-223, Klaipeda, Lithuania
Institute of Aquaculture and Protection of Waters, Faculty of Fisheries and Protection of Waters, South Bohemian Research Center of Aquaculture and Biodiversity of Hydrocenoses, University of South Bohemia in Ceske Budejovice, Na Sádkách 1780, 370 05, České Budějovice, Czech Republic
Faculty of Agricultural Sciences, Food Industry and Environmental Protection, Lucian Blaga University of Sibiu, Ron Ratiu street 5-7, Sibiu, Romania
Vijole Bradauskiene   

Food Institute, Kaunas University of Technology, Radvilenu road 19, 50254, Kaunas, Lithuania
Submission date: 2020-11-20
Final revision date: 2021-01-12
Acceptance date: 2021-01-26
Online publication date: 2021-02-12
Publication date: 2021-02-12
Due to the increasing incidence of gluten intolerance, researchers are focusing on finding ways to eliminate immunotoxicity of wheat, this would allow the use of wheat products for gluten-intolerant consumers. The article reviews recent studies on biotechnological methods to eliminate and reduce the immunogenicity of wheat products. So far, many gluten removal methods have been proposed, but their efficacy levels were quite different. Enzymatic treatment of gluten fragments can be considered the simplest and non-invasive tool to eliminate the toxicity of gliadins and glutenins. For this purpose, various endogenous enzymes derived from cereals, and also those of bacterial, fungal, plant, and animal origin can be used in food processing. Some of the enzymes hydrolyze gluten, others block the action of toxic protein fragments. The majority of studies were carried out using lactic acid bacteria cultures, as single strains or in consortia. Satisfactory results have been achieved using bacterial and plant enzymes, but the complete elimination of gluten immunogenicity is still possible by using fungal proteases, engineered enzymes or combining several treatments, for example, by using lactic acid fermentation or germination with fungal proteases. However, the question of how degradation of gluten affects the quality of flour (dough) in practice remains unanswered. It is not clear whether the products of such wheat flour are better and safer than those made from starches and whether their price and quality are acceptable to consumers. The insights presented in this review will be helpful to other researchers and cereal-based food producers in choosing ways to reduce gluten immunogenicity.
CD: coeliac disease; GF: gluten-free; GFD: gluten-free diet; HLA: human leukocyte antigen; LAB: lactic acid bacteria; NCGS: non-coeliac gluten sensitivity; PEP: prolyl endopeptidase; WA: wheat allergies.
Aaron, L., Torsten, M. (2019). Microbial transglutaminase: A new potential player in celiac disease. Clinical Immunology, 199, 37–43.
Adrianos, S.L., Mattioni, B., Tilley, M. (2017). Confirmation of gluten-free status of wheatgrass (Triticum aestivum). Quality Assurance and Safety of Crops & Foods, 9(1), 123–128.
Alvarez-Sieiro, P., Martin, M.C., Redruello, B., Del Rio, B., Ladero, V., Palanski, B.A., Khosla, C., Fernandez, M., Alvarez, M.A. (2014). Generation of food-grade recombinant Lactobacillus casei delivering Myxococcus xanthus prolyl endopeptidase. Applied Microbiology and Biotechnology, 98(15), 6689–6700.
Amirdivani, S., Khorshidian, N., Fidelis, M., Granato, D., Koushki, M.R., Mohammadi, M., Khoshtinat, K., Mortazavian, A.M. (2018). Effects of transglutaminase on health properties of food products. Current Opinion in Food Science, 22, 74–80.
Arte, E., Rizzello, C.G., Verni, M., Nordlund, E., Katina, K., Coda, R. (2015). Impact of enzymatic and microbial bioprocessing on protein modification and nutritional properties of wheat bran. Journal of Agricultural and Food Chemistry, 63(39), 8685–8693.
Baranzelli, J., Kringel, D.H., Colussi, R., Paiva, F.F., Aranha, B.C., de Miranda, M.Z., Zavareze, E. da R., Dias, A.R.G. (2018). Changes in enzymatic activity, technological quality and gamma-aminobutyric acid (GABA) content of wheat flour as affected by germination. LWT – Food Science and Technology, 90, 483–490.
Bassi, N.D. (2016). Gluten-free starch and methods of producing the same. U.S. Patent Application No. 15/193, 622.
Bellir, N., Bellir, M.N., Rouabah, L. (2014). Enzymatic degradation of gliadin by Nigella sativa seeds protease: Implications for new treatment of celiac disease. World Journal of Pharmacy Sciences, 3(12), 1555–1571.
Boukid, F., Mejri, M., Pellegrini, N., Sforza, S., Prandi, B. (2017a). How looking for celiac‐safe wheat can influence its technological properties. Comprehensive Reviews in Food Science and Food Safety, 16(5), 797–807.
Boukid, F., Prandi, B., Buhler, S., Sforza, S. (2017b). Effectiveness of germination on protein hydrolysis as a way to reduce adverse reactions to wheat. Journal of Agricultural and Food Chemistry, 65(45), 9854–9860.
Bromilow, S., Gethings, L.A., Buckley, M., Bromley, M., Shewry, P.R., Langridge, J.I., Mills, E.C. (2017). A curated gluten protein sequence database to support development of proteomics methods for determination of gluten in gluten-free foods. Journal of Proteomics, 163, 67–75.
Bruins Slot, I.D., Bremer, M.G.E.G., Hamer, R.J., van der Fels-Klerx, H.J. (2015). Part of celiac population still at risk despite current gluten thresholds. Trends in Food Science & Technology, 43(2), 219–226.
Brzozowski, B., Stasiewicz, K., Ostolski, M., Adamczak, M. (2020). Reducing immunoreactivity of gliadins and coeliac-toxic peptides using peptidases from L. acidophilus 5e2 and A. niger. Catalysts, 10(8), art no. 923.
Buddrick, O., Cornell, H.J., Small, D.M. (2015). Reduction of toxic gliadin content of wholegrain bread by the enzyme caricain. Food Chemistry, 170, 343–347.
Cao, W., Baumert, J.L., Downs, M.L. (2020). Evaluation of N-terminal labeling mass spectrometry for characterization of partially hydrolyzed gluten proteins. Journal of Proteomics, 210, art. no. 103538.
Cardone, G., D'Incecco, P., Pagani, M.A., Marti, A. (2020). Sprouting improves the bread‐making performance of whole wheat flour (Triticum aestivum L.). Journal of the Science of Food and Agriculture, 100(6), 2453–2459.
Catassi, C., Elli, L., Bonaz, B., Bouma, G., Carroccio, A., Castillejo, G., Cellier, C., Cristofori, F., de Magistris, L., Dolinsek, J., Dieterich, W., Francavilla, R., Hadjivassiliou, M., Holtmeier, W., Körner, U., Leffler, D.A., Lundin, K.E.A., Mazzarella, G., Mulder, C.J., Fasano, A. (2015). Diagnosis of non-celiac gluten sensitivity (NCGS): the Salerno experts’ criteria. Nutrients, 7(6), 4966–4977.
Cavaletti, L., Taravella, A., Carrano, L., Carenzi, G., Sigurtà, A., Solinas, N., De Caro, S., Di Stasio, L., Picascia, S., Laezza, M., Troncone, R., Gianfrani, C., Mamone, G. (2019). E40, a novel microbial protease efficiently detoxifying gluten proteins, for the dietary management of gluten intolerance. Scientific Reports, 9(1), art. no. 13147.
Chishty, S., Singh, N. (2017). Nutritional status of celiac and non-celiac children from Rajasthan, India. Nutrition & Food Science, 47(2), 240–253.
Cruz-Chamorro, I., Álvarez-Sánchez, N., Santos-Sánchez, G., Pedroche, J., Fernández-Pachón, M.S., Millán, F., Millán-Linares, M.C., Lardone, P.J., Bejarano, I., Guerrero, J.M., Carrillo-Vico, A. (2020). Immunomodulatory and antioxidant properties of wheat gluten protein hydrolysates in human peripheral blood mononuclear cells. Nutrients, 12(6), art no. 1673.
Curiel, J.A., Coda, R., Limitone, A., Katina, K., Raulio, M., Giuliani, G., Rizzello, C.G., Gobbetti, M. (2014). Manufacture and characterization of pasta made with wheat flour rendered gluten-free using fungal proteases and selected sourdough lactic acid bacteria. Journal of Cereal Science, 59(1), 79–87.
De Almeida, N.E.C., Esteves, F.G., dos Santos-Pinto, J.R.A., Peres De Paula, C., Da Cunha, A.F., Malavazi, I., Palma, M.S., Rodrigues-Filho, E. (2020). Digestion of intact dluten proteins by bifidobacterium species: reduction of cytotoxicity and proinflammatory responses. Journal of Agricultural and Food Chemistry, 68(15), 4485–4492.
De Angelis, M., Rizzello, C.G., Fasano, A., Clemente, M.G., De Simone, C., Silano, M., De Vincenzi, M., Losito, I., Gobbetti, M. (2006). VSL# 3 probiotic preparation has the capacity to hydrolyze gliadin polypeptides responsible for celiac sprue probiotics and gluten intolerance. Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease, 1762(1), 80–93.
Delgado-Povedano, M.M., De Castro, M.L. (2015). A review on enzyme and ultrasound: A controversial but fruitful relationship. Analytica Chimica Acta, 889, 1–21.
Diaz-Mendoza, M., Diaz, I., Martinez, M. (2019). Insights on the proteases involved in barley and wheat grain germination. International Journal of Molecular Sciences, 20(9), 2087–2098.
Di Cagno, R., Barbato, M., Di Camillo, C., Rizzello, C.G., De Angelis, M., Giuliani G., De Vincenzi, M., Gobbetti, M., Cucchiara, S. (2010). Gluten-free sourdough wheat baked goods appear safe for young celiac patients: a pilot study. Journal of Pediatric Gastroenterology and Nutrition, 51(6), 777–783.
Di Cagno, R., De Angelis, M., Auricchio, S., Greco, L., Clarke, C., De Vincenzi, M., Giovannini, C., D’Archivio, M., Landolfo, F., Parrilli, G., Minervini, F., Arendt, E., Gobbetti, M. (2004). Sourdough bread made from wheat and nontoxic flours and started with selected Lactobacilli is tolerated in celiac sprue patients. Applied and Environmental Microbiology, 70, 1088–1096.
Di Cagno, R., De Angelis, M., Lavermicocca, P., De Vincenzi, M., Giovannini, C., Faccia, M., Gobbetti, M. (2002). Proteolysis by sourdough lactic acid bacteria: effects on wheat flour protein fractions and gliadin peptides involved in human cereal intolerance. Applied and Environmental Microbiology, 68(2), 623–633.
Di Cagno, R., Rizzello, C.G., De Angelis, M., Cassone, A., Giuliani, G., Benedusi, A., Limitone, A., Surico, R.F., Gobbetti, M. (2008). Use of selected sourdough strains of Lactobacillus for removing gluten and enhancing the nutritional properties of gluten-free bread. Journal of Food Protection, 71(7), 1491–1495.
Ding, J., Hou, G.G., Nemzer, B.V., Xiong, S., Dubat, A., Feng, H. (2018). Effects of controlled germination on selected physicochemical and functional properties of whole-wheat flour and enhanced γ-aminobutyric acid accumulation by ultrasonication. Food Chemistry, 243, 214–221.
Do Nascimento, A.B., Fiates, G.M.R., Teixeira, E. (2017). We want to be normal! Perceptions of a group of Brazilian consumers with coeliac disease on gluten-free bread buns. International Journal of Gastronomy and Food Science, 7, 27–31.
Ehren, J., Morón, B., Martin, E., Bethune, M.T., Gray, G.M., Khosla, C. (2009). A food-grade enzyme preparation with modest gluten detoxification properties. PloS ONE, 4(7), art. no. e6313.
El-Ghaish, S., Ahmadova, A., Hadji-Sfaxi, I., El Mecherfi, K.E., Bazukyan, I., Choiset, Y., Rabesona, H., Sitohy, M., Popov, Y.G., Kuliev, A.A., Mozzi, F., Chobert, J.M., Haertlé, T. (2011). Potential use of lactic acid bacteria for reduction of allergenicity and for longer conservation of fermented foods. Trends in Food Science & Technology, 22(9), 509–516.
Engström, N., Sandberg, A.S., Scheers, N. (2015). Sourdough fermentation of wheat flour does not prevent the interaction of transglutaminase 2 with α2-gliadin or gluten. Nutrients, 7(4), 2134–2144.
Estévez, V., Ayala, J., Vespa, C., Araya, M. (2016). The gluten-free basic food basket: a problem of availability, cost and nutritional composition. European Journal of Clinical Nutrition, 70(10), 1215–1217.
FAOSTAT, [dataset] Production/Yield quantities of Wheat in World + (Total). (2020). Food and Agriculture Organization [].
Francavilla, R., De Angelis, M., Rizzello, C.G., Cavallo, N., Dal Bello, F., Gobbetti, M. (2017). Selected probiotic lactobacilli have the capacity to hydrolyze gluten peptides during simulated gastrointestinal digestion. Applied and Environmental Microbiology, 83(14), art no. e0036-37.
Fu, W., Xue, W., Liu, C., Tian, Y., Zhang, K., Zhu, Z. (2020). Screening of Lactic Acid Bacteria and yeasts from sourdough as starter cultures for reduced allergenicity wheat products. Foods, 9(6), 751–761.
Gabr, G.A. (2018). Extraction and purification of protease from Nigella sativa for its potential use in celiac disease. Asian Journal of Biotechnology and Bioresource Technology, 8(3), 1–9.
Gänzle, M.G., Loponen, J., Gobbetti, M. (2008). Proteolysis in sourdough fermentations: mechanisms and potential for improved bread quality. Trends in Food Science & Technology, 19(10), 513–521.
Gerez, C.L., Dallagnol, A., Rollán, G., de Valdez, G.F. (2012). A combination of two lactic acid bacteria improves the hydrolysis of gliadin during wheat dough fermentation. Food Microbiology, 32(2), 427–430.
Gerez, C.L., Font de Valdez, G., Rollan, G.C. (2008). Functionality of lactic acid bacteria peptidase activities in the hydrolysis of gliadin‐like fragments. Letters in Applied Microbiology, 47(5), 427–432.
Geßendorfer, B., Hartmann, G., Wieser, H., Koehler, P. (2011). Determination of celiac disease-specific peptidase activity of germinated cereals. European Food Research and Technology, 232(2), 205–209.
Gianfrani, C., Mamone, G., La Gatta, B., Camarca, A., Di Stasio, L., Maurano, F., Picascia, S., Capozzi, V., Perna, G., Picariello, G., Di Luccia, A. (2017). Microwave-based treatments of wheat kernels do not abolish gluten epitopes implicated in celiac disease. Food and Chemical Toxicology, 101, 105–113.
Giménez, M.J., Sánchez-León, S., Barro, F., García-Molina, M.D. (2019). Gluten free wheat: Are we there?. Nutrients, 11(3), art no. 487.
Giuliani, G., Benedusi, A., Di Cagno, R., Rizzello, C.G., De Angelis, M., Gobbetti, M., Cassone, A. (2016). Process of microbic biotechnology for completely degrading gluten in flours. U.S. Patent No. 9,386,777. Washington, U.S.A.
Giorgi, A., Cerrone, R., Capobianco, D., Filardo, S., Mancini, P., Fanelli, S., Mastromarino, P., Mosca, L. (2020). A probiotic preparation hydrolyzes gliadin and protects intestinal cells from the toxicity of pro-inflammatory peptides. Nutrients, 12(2), 495, 1–13.
Gobbetti, M., De Angelis, M., Di Cagno, R., Calasso, M., Archetti, G., Rizzello, C.G. (2019). Novel insights on the functional/nutritional features of the sourdough fermentation. International Journal of Food Microbiology, 302, 103–113.
Gordon, S.R., Stanley, E.J., Wolf, S., Toland, A., Wu, S.J., Hadidi, D., Siegel, J.B. (2012). Computational design of an α-gliadin peptidase. Journal of the American Chemical Society, 134(50), 20513–20520.
Greco, L., Gobbetti, M., Auricchio, R., Di Mase, R., Landolfo, F., Paparo, F., Di Cagno R., De Angelis, M., Rizzello, C.G., Cassone, A., Terrone, G., Timpone, L., D'Aniello, M., Maglio M., Troncone, R., Auricchio, S. (2011). Safety for patients with celiac disease of baked goods made of wheat flour hydrolyzed during food processing. Clinical Gastroenterology and Hepatology, 9(1), 24–29.
Grover, S., Kaur, S., Gupta, A.K., Taggar, G.K., Kaur, J. (2018). Characterization of trypsin like protease from Helicoverpa armigera (Hubner) and its potential inhibitors. Proceedings of the National Academy of Sciences, India Section B: Biological Sciences, 88(1), 49–56.
Guerdrum, L.J., Bamforth, C.W. (2012). Prolamin levels through brewing and the impact of prolyl endoproteinase. Journal of the American Society of Brewing Chemists, 70(1), 35–38.
Gutiérrez, S., Pérez-Andrés, J., Martínez-Blanco, H., Ferrero, M.A., Vaquero, L., Vivas, S., Casqueiro, J., Rodríguez-Aparicio, L.B. (2017). The human digestive tract has proteases capable of gluten hydrolysis. Molecular Metabolism, 6(7), 693–702.
Hartmann, G., Koehler, P., Wieser, H. (2006). Rapid degradation of gliadin peptides toxic for coeliac disease patients by proteases from germinating cereals. Journal of Cereal Science, 44(3), 368–371.
Heredia-Sandoval, N.G., Valencia-Tapia, M.Y., Calderón de la Barca, A.M., Islas-Rubio, A.R. (2016). Microbial proteases in baked goods: modification of gluten and effects on immunogenicity and product quality. Foods, 5(3), art no. 59.
Hopkins, S., Soon, J.M. (2019). Nutritional quality, cost and availability of gluten-free food in England. British Food Journal, 121(11), 2867–2882.
Islam, M.N., Zhang, M., Adhikari, B. (2014). The inactivation of enzymes by ultrasound – a review of potential mechanisms. Food Reviews International, 30(1), 1–21.
Janssen, G., Christis, C., Kooy-Winkelaar, Y., Edens, L., Smith, D., van Veelen, P., Koning, F. (2015). Ineffective degradation of immunogenic gluten epitopes by currently available digestive enzyme supplements. PLoS ONE, 10(6), art. no. e0128065.
Jayawardana, I.A., Montoya, C.A., McNabb, W.C., Boland, M.J. (2019). Possibility of minimizing gluten intolerance by co-consumption of some fruits – A case for positive food synergy? Trends in Food Science & Technology, 94, 91–97.
Jouanin, A., Gilissen, L.J., Boyd, L.A., Cockram, J., Leigh, F.J., Wallington, E.J., van den Broeck, H.C., van der Meer, I.M., Schaart, J.G., Visser, R.G.F., Smulders, M.J.M. (2018). Food processing and breeding strategies for coeliac-safe and healthy wheat products. Food Research International, 110, 11–21.
Katina, K., Heiniö, R.L., Autio, K., Poutanen, K. (2006). Optimization of sourdough process for improved sensory profile and texture of wheat bread. LWT – Food Science and Technology, 39(10), 1189–1202.
Kaur, L., Rutherfurd, S.M., Moughan, P.J., Drummond, L., Boland, M.J. (2010). Actinidin enhances protein digestion in the small intestine as assessed using an in vitro digestion model. Journal of Agricultural and Food Chemistry, 58(8), 5074–5080.
Kerpes, R., Knorr, V., Procopio, S., Koehler, P., Becker, T. (2016). Gluten-specific peptidase activity of barley as affected by germination and its impact on gluten degradation. Journal of Cereal Science, 68, 93–99.
King, J.A., Jeong, J., Underwood, F.E., Quan, J., Panaccione, N., Windsor, J.W., Ronksley, P., Shaheen, A.M., Quan, H., Van, S.V. (2020). Incidence of celiac disease is increasing over time: a systematic review and meta-analysis. American Journal of Gastroenterology, 115(4), 507–525.
Kiyosaki, T., Asakura, T., Matsumoto, I., Tamura, T., Terauchi, K., Funaki, J., Kuroda M., Misaka T., Abe, K. (2009). Wheat cysteine proteases triticain α, β and γ exhibit mutually distinct responses to gibberellin in germinating seeds. Journal of Plant Physiology, 166(1), 101–106.
Knorr, V., Wieser, H., Koehler, P. (2016). Production of gluten-free beer by peptidase treatment. European Food Research and Technology, 242(7), 1129–1140.
Krigel, A., Lebwohl, B. (2016). Nonceliac gluten sensitivity. Advances in Nutrition, 7(6), 1105–1110.
Kumar Mohan, B.V., Sarabhai, S., Prabhasankar, P. (2019). Targeted degradation of gluten proteins in wheat flour by prolyl endoprotease and its utilization in low immunogenic pasta for gluten sensitivity population. Journal of Cereal Science, 87, 59–67.
Kwiatkowska, B., Bennett, J., Akunna, J., Walker, G.M., Bremner, D.H. (2011). Stimulation of bioprocesses by ultrasound. Biotechnology Advances, 29(6), 768–780.
Laatikainen, R., Koskenpato, J., Hongisto, S.M., Loponen, J., Poussa, T., Huang, X., Sontag-Strohm, T., Salmenkari, H., Korpela, R. (2017). Pilot study: Comparison of sourdough wheat bread and yeast-fermented wheat bread in individuals with wheat sensitivity and irritable bowel syndrome. Nutrients, 9(11), art no. 1215.
Lamacchia, C., Landriscina, L., D’Agnello, P. (2016). Changes in wheat kernel proteins induced by microwave treatment. Food Chemistry, 197, 634–640.
Lerner, A., Matthias, T. (2015). Possible association between celiac disease and bacterial transglutaminase in food processing: a hypothesis. Nutrition Reviews, 73(8), 544–552.
Leszczynska, J., Łącka, A., Szemraj, J., Lukamowicz, J., Zegota, H. (2003). The effect of microwave treatment on the immunoreactivity of gliadin and wheat flour. European Food Research and Technology, 217(5), 387–391.
Li, Y., Yu, J., Goktepe, I., Ahmedna, M. (2016). The potential of papain and alcalase enzymes and process optimizations to reduce allergenic gliadins in wheat flour. Food Chemistry, 196, 1338–1345.
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, art no. 621.
Loponen, J., Sontag-Strohm, T., Venäläinen, J., Salovaara, H. (2007). Prolamin hydrolysis in wheat sourdoughs with differing proteolytic activities. Journal of Agricultural and Food Chemistry, 55(3), 978–984.
Lovegrove, A., Edwards, C.H., De Noni, I., Patel, H., El, S.N., Grassby, T., Zielke, CC., Ulmius, M., Nilsson, L., Butterworth, P.J., Ellis, P.R., Shewry, P.R. (2017). Role of polysaccharides in food, digestion, and health. Critical Reviews in Food Science and Nutrition, 57(2), 237–253.
Luongo, D., Maurano, F., Bergamo, P., Rossi, M. (2020). Microbial transglutaminase: A biotechnological tool to manage gluten intolerance. Analytical Biochemistry, 592, art. no. 113584.
Luz, C., D'Opazo, V., Mañes, J., Meca, G. (2019). Antifungal activity and shelf life extension of loaf bread produced with sourdough fermented by Lactobacillus strains. Journal of Food Processing and Preservation, 43(10), 1–8.
Mahroug, H., Ribeiro, M., Rhazi, L., Bentallah, L., Zidoune, M.N., Nunes, F.M., Igrejas, G. (2019). How microwave treatment of gluten affects its toxicity for celiac patients? A study on the effect of microwaves on the structure, conformation, functionality and immunogenicity of gluten. Food Chemistry, 297, art. no. 124986.
Mandile, R., Picascia, S., Parrella, C., Camarca, A., Gobbetti, M., Greco, L., Troncone, R., Gianfrani, C., Auricchio, R. (2017). Lack of immunogenicity of hydrolysed wheat flour in patients with coeliac disease after a short‐term oral challenge. Alimentary Pharmacology & Therapeutics, 46(4), 440–446.
Marino, M., Casale, R., Borghini, R., Di Nardi, S., Donato, G., Angeloni, A., Moscaritolo, S., Grasso, L., Mazzarella, G., Di Tola, M., Rossi, M., Picarelli, A. (2017). The effects of modified versus unmodified wheat gluten administration in patients with celiac disease. International Immunopharmacology, 47, 1–8.
Matthias, T., Jeremias, P., Neidhöfer, S., Lerner, A. (2016). The industrial food additive, microbial transglutaminase, mimics tissue transglutaminase and is immunogenic in celiac disease patients. Autoimmunity Reviews, 15(12), 1111–1119.
Matysiak–Budnik, T., Candalh, C., Cellier, C., Dugave, C., Namane, A., Vidal–Martinez, T., Cerf–Bensussan, N., Heyman, M. (2005). Limited efficiency of prolyl-endopeptidase in the detoxification of gliadin peptides in celiac disease. Gastroenterology, 129(3), 786–796.
McAllister, B.P., Williams, E., Clarke, K. (2019). A comprehensive review of celiac disease/gluten-sensitive enteropathies. Clinical Reviews in Allergy & Immunology, 57(2), 226–243.
Meshram, A., Singhal, G., Bhagyawant, S.S., Srivastava, N. (2019). Plant-derived enzymes: a treasure for food biotechnology. In M. Kuddus (Ed.), Enzymes in Food Biotechnology, Academic Press, London, UK, pp. 483–502.
Michalcová, E., Potocká, E., Chmelová, D., Ondrejovic, M. (2019). Study of wheat protein degradation during germination. The Journal of Microbiology, Biotechnology and Food Sciences, 1(6), 1437–1447.
Mickowska, B., Romanova, K., Socha, P., Urminska, D. (2018). Reduction of immunoreactivity of wheat and rye prolamins by Flavourzyme proteolysis. Journal of Food & Nutrition Research, 57(3), 307–314.
Mika, N., Gorshkov, V., Spengler, B., Zorn, H., Rühl, M. (2015). Characterization of novel insect associated peptidases for hydrolysis of food proteins. European Food Research and Technology, 240(2), 431–439.
Mitea, C., Havenaa, R., Drijfhout, J.W., Edens, L., Dekking, L., Koning, F. (2008). Efficient degradation of gluten by a prolyl endoprotease in a gastrointestinal model: implications for celiac disease. Gut, 57(1), 25–32.
Montemurro, M., Pontonio, E., Gobbetti, M., Rizzello, C.G. (2019). Investigation of the nutritional, functional and technological effects of the sourdough fermentation of sprouted flours. International Journal of Food Microbiology, 302, 47–58.
Montserrat, V., Bruins, M.J., Edens, L., Koning, F. (2015). Influence of dietary components on Aspergillus niger prolyl endoprotease mediated gluten degradation. Food Chemistry, 174, 440–445.
Moreno Amador, M.D.L., Arévalo-Rodríguez, M., Durán, E.M., Martínez Reyes, J.C., Sousa Martín, C. (2019). A new microbial gluten-degrading prolyl endopeptidase: Potential application in celiac disease to reduce gluten immunogenic peptides. PLoS ONE, 14(6), art. no. e0218346.
Naqash, F., Gani, A., Gani, A., Masoodi, F.A. (2017). Gluten-free baking: Combating the challenges – A review. Trends in Food Science & Technology, 66, 98–107.
Navarro, V., Del Pilar Fernández-Gil, M., Simón, E., Bustamante, M.Á. (2017). Gluten: general aspects and international regulations for products for celiac people. In: J. Miranda, E. Simón. (Eds.). Nutritional and Analytical Approaches of Gluten-Free Diet in Celiac Disease, Springer, Cham, Switzerland, pp. 15–27.
Nionelli, L., Rizzello, C.G. (2016). Sourdough-based biotechnologies for the production of gluten-free foods. Foods, 5(3), art. no. 65.
Patent application WO2006 / 097415, 2006. Mixture of at least 6 species of lactic acid bacteria and/or Bifidobacteria in the manufacture of sourdough.
Pellegrini, N., Agostoni, C. (2015). Nutritional aspects of gluten‐free products. Journal of the Science of Food and Agriculture, 95(12), 2380–2385.
Pilon, F.M., Silva, C.D.R., Visôtto, L.E., Barros, R.D.A., da Silva Júnior, N.R., Campos, W.G., de Almeida Oliveira, M.G. (2017). Purification and characterization of trypsin produced by gut bacteria from Anticarsia gemmatalis. Archives of Insect Biochemistry and Physiology, 96(2), art. no. e21407.
Rahaman, T., Vasiljevic, T., Ramchandran, L. (2016). Effect of processing on conformational changes of food proteins related to allergenicity. Trends in Food Science & Technology, 49, 24–34.
Rashmi, B.S., Gayathri, D., Vasudha, M., Prashantkumar, C.S., Swamy, C.T., Sunil, K.S., Somaraja, P.K., Prakash, P., Prakash, P. (2020). Gluten hydrolyzing activity of Bacillus spp. isolated from sourdough. Microbial Cell Factories, 19(1), art. no. 130.
Ravee, R., Salleh, F.I.M., Goh, H.H. (2018). Discovery of digestive enzymes in carnivorous plants with focus on proteases. PeerJ, 6, art. no. e4914.
Rey, M., Yang, M., Lee, L., Zhang, Y., Sheff, J.G., Sensen, C.W., Mrazek, H., Halada, P., Man, P., McCarville, J.L., Verdu, E.F., Schriemer, D.C. (2016). Addressing proteolytic efficiency in enzymatic degradation therapy for celiac disease. Scientific Reports, 6, art. no. 30980.
Rollan, G., De Angelis, M., Gobbetti, M., De Valdez, G.F. (2005). Proteolytic activity and reduction of gliadin‐like fractions by sourdough lactobacilli. Journal of Applied Microbiology, 99(6), 1495–1502.
Romanová, K., Urminská, D. (2017). Potential of Lactobacillus plantarum CCM 3627 and Lactobacillus brevis CCM 1815 for fermentation of cereal substrates. Potravinarstvo Slovak Journal of Food Sciences, 11(1), 544–549.
Rutherfurd, S.M., Montoya, C.A., Zou, M.L., Moughan, P.J., Drummond, L.N., Boland, M.J. (2011). Effect of actinidin from kiwifruit (Actinidia deliciosa cv. Hayward) on the digestion of food proteins determined in the growing rat. Food Chemistry, 129(4), 1681–1689.
Sakandar, H.A., Usman, K., Imran, M. (2018). Isolation and characterization of gluten-degrading Enterococcus mundtii and Wickerhamomyces anomalus, potential probiotic strains from indigenously fermented sourdough (Khamir). LWT – Food Science and Technology, 91, 271–277.
Salden, B.N., Monserrat, V., Troost, F.J., Bruins, M.J., Edens, L., Bartholomé, R., Haenen, G.R., Winkens, B., Koning, F., Masclee, A.A. (2015). Randomised clinical study: Aspergillus niger‐derived enzyme digests gluten in the stomach of healthy volunteers. Alimentary Pharmacology & Therapeutics, 42(3), 273–285.
Savvateeva, L.V., Gorokhovets, N.V., Makarov, V.A., Serebryakova, M.V., Solovyev, A.G., Morozov, S.Y., Reddy, V.P., Zernii, E.Y., Zamyatnin, A.A., Aliev, G. (2015). Glutenase and collagenase activities of wheat cysteine protease Triticain-α: feasibility for enzymatic therapy assays. The International Journal of Biochemistry & Cell Biology, 62, 115–124.
Scherf, K.A., Wieser, H., Koehler, P. (2018). Novel approaches for enzymatic gluten degradation to create high-quality gluten-free products. Food Research International, 110, 62–72.
Schräder, C.U., Lee, L., Rey, M., Sarpe, V., Man, P., Sharma, S., Zabrouskov, V., Larsen, B., Schriemer, D.C. (2017). Neprosin, a selective prolyl endoprotease for bottom-up proteomics and histone mapping. Molecular & Cellular Proteomics, 16(6), 1162–1171.
Schulz, K., Giesler, L., Linke, D., Berger, R.G. (2018). A prolyl endopeptidase from Flammulina velutipes for the possible degradation of celiac disease provoking toxic peptides in cereal proteins. Process Biochemistry, 73, 47–55.
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(6), 1161–1170.
Siow, H.L., Choi, S.B., Gan, C.Y. (2016). Structure–activity studies of protease activating, lipase inhibiting, bile acid binding and cholesterol-lowering effects of pre-screened cumin seed bioactive peptides. Journal of Functional Foods, 27, 600–611.
Socha, P., Mickowska, B., Urminská, D., Kacmárová, K. (2015). The use of different proteases to hydrolyze gliadins. The Journal of Microbiology, Biotechnology and Food Sciences, 4, 101–104.
Stănciuc, N., Banu, I., Bolea, C., Patraşcu, L., Aprodu, I. (2018). Structural and antigenic properties of thermally treated gluten proteins. Food Chemistry, 267, 43–51.
Standard 118–1979. Codex Standard for foods for special dietary use for persons intolerant to gluten. Codex Alimentarius Commission. Revision 2015,1. [http://www.codexalimentarius.n...].
Stantiall, S.E., Serventi, L. (2018). Nutritional and sensory challenges of gluten-free bakery products: a review. International Journal of Food Sciences and Nutrition, 69(4), 427–436.
Stazi, A.V., Trinti, B. (2008). Selenium deficiency in celiac disease: risk of autoimmune thyroid diseases. Minerva Medica, 99(6), 643–653.
Stefańska, I., Piasecka-Jóźwiak, K., Kotyrba, D., Kolenda, M., Stecka, K.M. (2016). Selection of lactic acid bacteria strains for the hydrolysis of allergenic proteins of wheat flour. Journal of the Science of Food & Agriculture, 96(11), 3897–3905.
Stenman, S.M., Venäläinen, J.I., Lindfors, K., Auriola, S., Mauriala, T., Kaukovirta-Norja, A., Jantunen, A., Laurila, K., Qiao, S.W., Sollid, L.M., Männistö P.T., Kaukinen, K. Mäki, M. (2009). Enzymatic detoxification of gluten by germinating wheat proteases: implications for new treatment of celiac disease. Annals of Medicine, 41(5), 390–400.
Stepniak, D., Spaenij-Dekking, L., Mitea, C., Moester, M., de Ru, A., Baak-Pablo, R., van Veelen, P., Edens L., Koning, F. (2006). Highly efficient gluten degradation with a newly identified prolyl endoprotease: implications for celiac disease. American Journal of Physiology-Gastrointestinal and Liver Physiology, 291(4), G621–G629.
Sun, L., Li, X., Zhang, Y., Yang, W., Ma, G., Ma, N., Hu, Q., Pei, F. (2020). A novel lactic acid bacterium for improving the quality and shelf life of whole wheat bread. Food Control, 109, art. no. 106914.
Sun, Q., Zhang, B., Yan, Q.J., Jiang, Z.Q. (2016). Comparative analysis on the distribution of protease activities among fruits and vegetable resources. Food Chemistry, 213, 708–713.
Taga, Y., Hayashida, O., Kusubata, M., Ogawa-Goto, K., Hattori, S. (2017). Production of a novel wheat gluten hydrolysate containing dipeptidyl peptidase-IV inhibitory tripeptides using ginger protease. Bioscience, Biotechnology and Biochemistry, 81(9), 1823–1828.
Tanveer, M., Ahmed, A. (2019). Non-celiac gluten sensitivity: A systematic review. Journal of the College of Physicians and Surgeons Pakistan, 29(1), 51–57.
Tavano, O.L., Berenguer‐Murcia, A., Secundo, F., Fernandez‐Lafuente, R. (2018). Biotechnological applications of proteases in food technology. Comprehensive Reviews in Food Science and Food Safety, 17(2), 412–436.
Tereshchenkova, V.F., Goptar, I.A., Kulemzina, I.A., Zhuzhikov, D.P., Serebryakova, M.V., Belozersky, M.A., Dunaevsky, Y.E., Oppert, B., Filippova, I.Y., Elpidina, E.N. (2016). Dipeptidyl peptidase 4 – an important digestive peptidase in Tenebrio molitor larvae. Insect Biochemistry and Molecular Biology, 76, 38–48.
Thiele, C., Grassl, S., Gänzle, M. (2004). Gluten hydrolysis and depolymerization during sourdough fermentation. Journal of Agricultural and Food Chemistry, 52(5), 1307–1314.
Thomason, W.E., Hughes, K.R., Griff, C.A., Parrish, D.J., Barbeau, W.E. (2019). Understanding pre-harvest sprouting of wheat. Publications, Virginia Cooperative Extension, 424, 424-060.
Toft-Hansen, H., Rasmussen, K.S., Staal, A., Roggen, E.L., Sollid, L.M., Lillevang, S.T., Barington, T., Husby, S. (2014). Treatment of both native and deamidated gluten peptides with an endo-peptidase from Aspergillus niger prevents stimulation of gut-derived gluten-reactive T cells from either children or adults with celiac disease. Clinical Immunology, 153(2), 323–331.
Tran, C.D., Katsikeros, R., Manton, N., Krebs, N.F., Hambidge, K.M., Butler, R.N., Davidson, G.P. (2011). Zinc homeostasis and gut function in children with celiac disease. The American Journal of Clinical Nutrition, 94, 1026–1032.
Vermeulen, N., Kretzer, J., Machalitza, H., Vogel, R.F., Gänzle, M.G. (2006). Influence of redox-reactions catalysed by homo-and hetero-fermentative lactobacilli on gluten in wheat sourdoughs. Journal of Cereal Science, 43(2), 137–143.
Vici, G., Belli, L., Biondi, M., Polzonetti, V. (2016). Gluten free diet and nutrient deficiencies: A review. Clinical Nutrition, 35(6), 1236–1241.
Vukotić, G., Strahinić, I., Begović, J., Lukić, J., Kojić, M., Fira, D. (2016). Survey on proteolytic activity and diversity of proteinase genes in mesophilic lactobacilli. Microbiology, 85(1), 33–41.
Walter, T., Wieser, H., Koehler, P. (2014). Production of gluten-free wheat starch by peptidase treatment. Journal of Cereal Science, 60(1), 202–209.
Wang, J.S., Zhao, M.M., Zhao, Q.Z., Jiang, Y.M. (2007). Antioxidant properties of papain hydrolysates of wheat gluten in different oxidation systems. Food Chemistry, 101(4), 1658–1663.
Watanabe, M., Watanabe, J., Sonoyama, K., Tanabe, S. (2000). Novel method for producing hypoallergenic wheat flour by enzymatic fragmentation of the constituent allergens and its application to food processing. Bioscience, Biotechnology, and Biochemistry, 64(12), 2663–2667.
Wieser, H., Koehler, P. (2012). Detoxification of gluten by means of enzymatic treatment. Journal of AOAC International, 95(2), 356–363.
Wolf, C., Siegel, J.B., Tinberg, C., Camarca, A., Gianfrani, C., Paski, S., Guan, R., Montelione, G., Baker, D., Pultz, I.S. (2015). Engineering of Kuma030: a gliadin peptidase that rapidly degrades immunogenic gliadin peptides in gastric conditions. Journal of the American Chemical Society, 137(40), 13106–13113.
Xue, L., Li, Y., Li, T., Pan, H., Liu, J., Fan, M., Qian, H., Zhang, H., Ying, H., Wang, L. (2019). Phosphorylation and enzymatic hydrolysis with alcalase and papain effectively reduce allergic reactions to gliadins in normal mice. Journal of Agricultural and Food Chemistry, 67(22), 6313–6323.
Yang, X., Li, Y., Li, S., Oladejo, A.O., Wang, Y., Huang, S., Zhou, C., Wang, Y., Mao, Li., Zhang, Y., Ma, H., Ye, X. (2017). Effects of multi-frequency ultrasound pretreatment under low power density on the enzymolysis and the structure characterization of defatted wheat germ protein. Ultrasonics Sonochemistry, 38, 410–420.
Yin, Y., Wang, J., Yang, S., Feng, J., Jia, F., Zhang, C. (2015). Protein degradation in wheat sourdough fermentation with Lactobacillus plantarum M616. Interdisciplinary Sciences: Computational Life Sciences, 7(2), 205–210.
Yoosuf, S., Makharia, G.K. (2019). Evolving therapy for celiac disease. Frontiers in Pediatrics, 7, art. no. 193.
Yu, Z.L., Zeng, W.C., Zhang, W.H., Liao, X.P., Shi, B. (2014). Effect of ultrasound on the activity and conformation of α-amylase, papain and pepsin. Ultrasonics Sonochemistry, 21(3), 930–936.
Zhang, H., Claver, I.P., Zhu, K.X., Zhou, H. (2011). The effect of ultrasound on the functional properties of wheat gluten. Molecules, 16(5), 4231–4240.
Zhang, Y., Ma, H., Wang, B., Qu, W., Li, Y., He, R., Wali, A. (2015). Effects of ultrasound pretreatment on the enzymolysis and structural characterization of wheat gluten. Food Biophysics, 10(4), 385–395.
Zhou, L., Wu, Y., Cheng, Y., Wang, J., Lu, J., Gao, J., Yuan, J., Chen, H. (2017). Blocking celiac antigenicity of the glutamine-rich gliadin 33-mer peptide by microbial transglutaminase. RSC Advances, 7(24), 14438–14447.