From a chemical perspective, gluten has been defined as the proteinaceous mass that remains when wheat dough is washed with water and consists primarily of the prolamin and glutelin fractions of the storage proteins of wheat.
Gluten proteins have long been of interest to the food industry due to their high impact on the baking quality of wheat flours. More specifically, gluten proteins are responsible for the high water absorption capacity and unique viscoelastic properties of wheat dough. From a chemical perspective, gluten has been defined as the proteinaceous mass that remains when wheat dough is washed with water and consists primarily of the prolamin and glutelin fractions of the storage proteins of wheat. The terms prolamin and glutelin originate from the classification of grain proteins into four fractions according to their solubility properties (Osborne fractions). Prolamins are insoluble in water but soluble in alcohol, whereas glutelins are insoluble in both water and alcohol. The terms gliadin and glutenin account for the prolamin and glutelin fractions of wheat, whereas the terms secalin, hordein and avenin describe the prolamin fraction of rye, barley and oats, respectively. Likewise, the glutelin fractions of rye and barley are commonly described as secalinin and hordenin, however, similar terminology does not apply for oat glutelins. Furthermore, prolamins are commonly grouped into fractions (α, γ, ω) characterized by different electrophoretic mobilities, whereas glutelins are classified into subunits on the background of their molecular weight. Codex Alimentarius has defined gluten as “a protein fraction from wheat, rye, barley, oats or their crossbred varieties and derivatives thereof, to which some persons are intolerant and that is insoluble in water and 0.5M NaCl”. As a result, gluten is nowadays considered to be a common term for the prolamin and glutelin fractions of wheat, rye, barley and, in some cases, oats.
Gluten proteins contain repetitive sequence sections that are rich in the amino acids proline and glutamine. Such sections cannot be fully degraded by the human gastrointestinal enzymes, resulting in the presence of relatively long gluten peptides in the small intestine. In patients with CD, such gluten peptides trigger an inflammatory reaction, however, their presence in the small intestine of most healthy individuals is believed to be rather unproblematic. In vitro studies using caco-2 cell lines as well as ex vivo studies on human biopsy explants from both CD patients and healthy controls (HCs), suggest that exposure to gliadin disrupts the integrity of the intestinal epithelium. The effect of gliadin on intestinal permeability is believed to be mediated through the secretion of the protein zonulin. Zonulin has been identified as prehaptoglobin-2 and serum zonulin is often used as a marker of intestinal permeability. Levels of zonulin have been found to be elevated in autoimmune diseases, however, widely used ELISA kits cross-react with proteins, such as properdin and complement C3, which shows why caution should be practiced when interpreting data on this topic. In addition, several publications using different methods have illustrated that gliadins can affect the intestinal permeability in non-genetically modified mice , however, the mechanism of action is rather unclear as mice do not have the haptoglobin-2 allele and therefore cannot express zonulin .
The entry is from 10.3390/nu12082316
- Shewry, P.R. Wheat. J. Exp. Bot. 2009, 60, 1537–1553.
- Koehler, P.; Wieser, H.; Konitzer, K. Gluten—The Precipitating Factor. In Celiac Disease and Gluten; Elsevier Inc.: San Diego, CA, USA, 2014; pp. 97–148.
- Velísek, J. Amino Acids, Peptides and Proteins. In The Chemistry of Food; WILEY Blackwell: Hoboken, NJ, USA, 2014; pp. 60–61.
- Belitz, H.-D.; Grosch, W.; Schieberle, P. Cereals and Cereal Products. In Food Chemistry, 4th ed; Belitz, H.-D., Grosch, W., Schieberle, P., Eds.; Springer: Berlin/Heidelberg, Germany, 2009; pp. 670–745.
- Kathrin Schalk; Barbara Lexhaller; Peter Koehler; Katharina Anne Scherf; Isolation and characterization of gluten protein types from wheat, rye, barley and oats for use as reference materials. PLoS ONE 2017, 12, e0172819, 10.1371/journal.pone.0172819.
- Katharina Anne Scherf; Peter Koehler; Herbert Wieser; Gluten and wheat sensitivities – An overview. Journal of Cereal Science 2016, 67, 2-11, 10.1016/j.jcs.2015.07.008.
- Codex Alimentarius International Food Standards. Standard for Foods for Special Dietary Use for Persons Intolerant to Gluten Codex Stan 118-1979; 2008; pp. 1–5. Available online: https://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=&cad=rja&uact=8&ved=2ahUKEwjj6ZPvxvjqAhXpkYsKHQ45DPUQFjAAegQIBRAB&url=http%3A%2F%2Fwww.fao.org%2Finput%2Fdownload%2Fstandards%2F291%2FCXS_118e_2015.pdf&usg=AOvVaw3j2IOMnRs176g2GN-tOyUH (accessed on 1 August 2020).
- Herbert Wieser; Chemistry of gluten proteins. Food Microbiology 2007, 24, 115-119, 10.1016/j.fm.2006.07.004.
- Sander, G.R.; Cummins, A.G.; Henshall, T.; Powell, B.C. Rapid disruption of intestinal barrier function by gliadin involves altered expression of apical junctional proteins. FEBS Lett. 2005, 579, 4851–4855.
- Drago, S.; El Asmar, R.; Di Pierro, M.; Grazia Clemente, M.; Tripathi, A.; Sapone, A.; Thakar, M.; Iacono, G.; Carroccio, A.; D’Agate, C.; et al. Gliadin, zonulin and gut permeability: Effects on celiac and non-celiac intestinal mucosa and intestinal cell lines. Scand. J. Gastroenterol. 2006, 41, 408–419.
- Justin Hollon; Elaine Leonard Puppa; Bruce Greenwald; Eric Goldberg; Anthony L. Guerrerio; Alessio Fasano; Effect of Gliadin on Permeability of Intestinal Biopsy Explants from Celiac Disease Patients and Patients with Non-Celiac Gluten Sensitivity. Nutrients 2015, 7, 1565-1576, 10.3390/nu7031565.
- Karen M. Lammers; Ruliang Lu; Julie Brownley; Bao Lu; Craig Gerard; Karen Thomas; Prasad Rallabhandi; Terez Shea-Donohue; Amir Tamiz; Sefik Alkan; et al. Gliadin Induces an Increase in Intestinal Permeability and Zonulin Release by Binding to the Chemokine Receptor CXCR3. Gastroenterology 2008, 135, 194.e3-204.e3, 10.1053/j.gastro.2008.03.023.
- Amit Tripathi; Karen M. Lammers; Simeon Goldblum; Terez Shea-Donohue; Sarah Netzel-Arnett; Marguerite S. Buzza; Toni M. Antalis; Stefanie N. Vogel; Aiping Zhao; Shiqi Yang; et al. Identification of human zonulin, a physiological modulator of tight junctions, as prehaptoglobin-2. Proceedings of the National Academy of Sciences 2009, 106, 16799-16804, 10.1073/pnas.0906773106.
- Sapone, A.; de Magistris, L.; Pietzak, M.; Clemente, M.G.; Tripathi, A.; Cucca, F.; Lampis, R.; Kryszak, D.; Cartenì, M.; Generoso, M.; et al. Zonulin upregulation is associated with increased gut permeability in subjects with type 1 diabetes and their relatives. Diabetes 2006, 55, 1443–1449.
- Aydin, B.K.; Yildiz, M.; Akgun, A.; Topal, N.; Adal, E.; Onal, H. Children with Hashimoto’s Thyroiditis Have Increased Intestinal Permeability: Results of a Pilot Study. J. Clin. Res. Pediatric Endocrinol. 2020.
- Caviglia, G.P.; Dughera, F.; Ribaldone, D.G.; Rosso, C.; Abate, M.L.; Pellicano, R.; Bresso, F.; Smedile, A.; Saracco, G.M.; Astegiano, M. Serum zonulin in patients with inflammatory bowel disease: A pilot study. Minerva Med. 2019, 110, 95–100.
- Fasano, A. All disease begins in the (leaky) gut: Role of zonulin-mediated gut permeability in the pathogenesis of some chronic inflammatory diseases. F1000 Res. 2020, 9.
- Ajamian, M.; Steer, D.; Rosella, G.; Gibson, P.R. Serum zonulin as a marker of intestinal mucosal barrier function: May not be what it seems. PLoS ONE 2019, 14, e0210728.
- Scheffler, L.; Crane, A.; Heyne, H.; Tönjes, A.; Schleinitz, D.; Ihling, C.H.; Stumvoll, M.; Freire, R.; Fiorentino, M.; Fasano, A.; et al. Widely Used Commercial ELISA Does Not Detect Precursor of Haptoglobin2, but Recognizes Properdin as a Potential Second Member of the Zonulin Family. Front. Endocrinol. 2018, 9, 22.
- Sunao Shimada; Tetsuya Tanigawa; Toshio Watanabe; Akinobu Nakata; Naoki Sugimura; Shigehiro Itani; Akira Higashimori; Yuji Nadatani; Koji Otani; Koichi Taira; et al. Involvement of gliadin, a component of wheat gluten, in increased intestinal permeability leading to non-steroidal anti-inflammatory drug-induced small-intestinal damage. PLoS ONE 2019, 14, e0211436, 10.1371/journal.pone.0211436.
- Li Zhang; Daniel Andersen; Henrik Munch Roager; Martin Iain Bahl; Camilla H. F. Hansen; Niels Danneskiold-Samsøe; Karsten Kristiansen; Ilinca Daria Radulescu; Christian Sina; Henrik Lauritz Frandsen; et al. Effects of Gliadin consumption on the Intestinal Microbiota and Metabolic Homeostasis in Mice Fed a High-fat Diet. Scientific Reports 2017, 7, 44613, 10.1038/srep44613.
- Karen M. Lammers; Ruliang Lu; Julie Brownley; Bao Lu; Craig Gerard; Karen Thomas; Prasad Rallabhandi; Terez Shea-Donohue; Amir Tamiz; Sefik Alkan; et al. Gliadin Induces an Increase in Intestinal Permeability and Zonulin Release by Binding to the Chemokine Receptor CXCR3. Gastroenterology 2008, 135, 194-204.e3, 10.1053/j.gastro.2008.03.023.
- Craig Sturgeon; Jinggang Lan; Alessio Fasano; Zonulin transgenic mice show altered gut permeability and increased morbidity/mortality in the DSS colitis model.. Annals of the New York Academy of Sciences 2017, 1397, 130-142, 10.1111/nyas.13343.