Oat (Avena sativa L.) is considered to be a healthy food. In contrast to other grain crops, oat is high in protein, lipids, dietary fiber, antioxidants, and uniquely in avenanthramides. The question of whether it can also be consumed by people suffering from celiac disease is still unresolved. The main aim of this study was to extract and sequence genes for potentially harmful avenins, globulins, and α-amylase/trypsin inhibitors in six oat varieties and to establish their variability using PacBio sequencing technology of enriched libraries. The results were compared with sequences of the genes already present in databases. In total, 21 avenin, 75 globulin, and 25 α-amylase/trypsin inhibitor genes were identified and mapped in the hexaploid oat chromosomes. In all of the three gene families, only marginal sequence differences were found between the oat varieties within the individual genes. Avenin epitopes were found in all four types of avenin genes occurring in all oat varieties tested within this study. However, the number of avenin genes was nearly four times lower than of globulin genes and, on the protein level, formed only 10% of storage proteins. Therefore, the question of whether oat is safe to celiac disease people is a question of boundary values.

Crop Research Institute Drnovská 507 Prague 6 Ruzyne Czech Republic

See more in PubMed

Balakireva AV, Zamyatnin AAJ. Properties of gluten intolerance: Gluten structure, evolution, pathogenicity and detoxification capabilities. Nutrients. 2016;8:644. doi: 10.3390/nu8100644. PubMed DOI PMC

Sharma N, Bhatia S, Chunduri V, Kaur S, Sharma S, Kapoor P, Kumari A, Garg M. Pathogenesis of celiac disease and other gluten related disorders in wheat and strategies for mitigating them. Front. Nutr. 2020;7:6. doi: 10.3389/fnut.2020.00006. PubMed DOI PMC

Haboubi NY, Taylor S, Jones S. Coeliac disease and oats: a systematic review. Postgrad. Med. J. 2006;82:672–678. doi: 10.1136/pgmj2006.045443. PubMed DOI PMC

Rashh V, Magris R, Cannizzaro R. New insights into the pathogenesis of celiac disease. Front. Med. 2017;4:137. doi: 10.3389/fmed.2017.00137. PubMed DOI PMC

Arentz-Hansen H, Fleckenstein B, Molberg Ø, Scott H, Koning F, Jung G, Roepstorff P, Lundin KEA, Sollid LM. The molecular basis for oat intolerance in patients with celiac disease. PLOS Med. 2004;1:1. doi: 10.1371/journal.pmed.0010001. PubMed DOI PMC

Singh P, Arora A, Strand TA, Leffler DA, Catassi C, Green PH. Global prevalence of celiac disease systematic review and meta-analysis. Clin. Gastroenterol. Hepatol. 2018;16:823–836. doi: 10.1016/j.cgh.2017.06.037. PubMed DOI

Ahmad M, Gul-Zaffar ZA, Habib M. A review on oat (Avena sativa L.) as a dual-purpose crop. Sci. Res. Essays. 2014;9(4):52–59. doi: 10.5897/SRE2014.5820. DOI

Rasane P, Jha A, Sabikhi L, Kumar A, Unnikrishnan VS. Nutritional advantages of oats and opportunities for its processing as value added Foods: A review. J. Food Sci. Technol. 2015;52(2):662–675. doi: 10.1007/s13197-013-1072-1. PubMed DOI PMC

Gilissen LJWJ, van der Meer IM, Smulders MJM. Why oats are safe and healthy for celiac disease patients. Med. Sci. 2016;4:21. doi: 10.3390/medsci4040021. PubMed DOI PMC

Real A, Comino I, Lorenzo L, Merchán F, Gil-Humanes J, Giménez MJ, López-Casado MA, Torres MI, Cebolla A, Sousa C, Barro F, Pistón F. Molecular and immunological characterization of gluten proteins isolated from oat cultivars that differ in toxicity for celiac disease. PLoS ONE. 2012;7(12):e48365. doi: 10.1371/journal.pone.0048365. PubMed DOI PMC

Chesnut RS, Shotwell MA, Boyer SK, Larkins BA. Analysis of avenin proteins and the expression of their mRNAs in developing oat seeds. Plant Cell. 1989;1:913–924. PubMed PMC

Comino I, Bernardo D, Bancel E, de Lourdes Moreno M, Sánchez B, Barro F, Šuligoj T, Ciclitira PJ, Cebolla A, Knight SC, Branlard G, Sousa C. Identification and molecular characterization of oat peptides implicated on celiac response. Food Nutr. Res. 2016;60:30324. doi: 10.3402/fnr.v60.30324. PubMed DOI PMC

Tye-Din JA, Stewart JA, Dromey JA, Beissbarth T, Van Heel DA, Tatham A, et al. Comprehensive, quantitative mapping of T cell epitopes in gluten in celiac disease. Sci. Transl. Med. 2010;2:1–14. doi: 10.1126/scitranslmed.3001012. PubMed DOI

Ballabio C, Uberti F, Manferdelli S, Vacca E, Boggini G, Redaelli R, Catassi C, Lionetti E, Penas E, Restani P. Molecular characterization of 36 oat varieties and in vitro assessment of their suitability for celiac diet. J. Cereal Sci. 2011;54:110–115. doi: 10.1016/j.jcs.2011.04.004. DOI

Londono DM, Westende WPC, Goryunova S, Salentijn EMJ, van den Broeck HC, van der Meer LM, Visser RGF, Gilissen LJWJ, Smulders MJM. Avenin diversity analysis of the genus Avena (oat) Relevance for people with celiac disease. J. Cereal Sci. 2013;58:170–177. doi: 10.1016/j.jcs.2013.03.017. DOI

Kosová K, Leišová-Svobodová L, Dvořáček V. Oats as a safe alternative to Triticeae cereals for people suffering from celiac disease? A review. Plant Foods Hum. Nutr. 2020;75:131–141. doi: 10.1007/s11130-020-00800-8. PubMed DOI

Tuire I, Marja-Leena L, Teea S, Katri H, Jukka P, Päivi S. Persistent duodenal intraepithelial lymphocytosis despite a long term strict gluten-free diet in celiac disease. Am. J. Gastroenterol. 2012;107:1563–1569. doi: 10.1038/ajg.2012.220. PubMed DOI

Mujico JR, Mitea C, Gilissen LJWJ, de Ru A, van Veelen P, Smulders MJM, Koning F. Natural variation in avenin epitopes among oat varieties: implications for celiac disease. J. Cereal Sci. 2011;54:8–12. doi: 10.1016/j.jcs.2010.09.007. DOI

Gazza L, Gazzelloni G, Taddaei F, Latini A, Muccilli V, Alfieri M, Conti S, Redaelli R, Pogna NE. The starch-bound alpha-amylase/trypsin-inhibitors in Avena. Mol. Genet. Genom. 2016;291:2043–2054. doi: 10.1007/s00438-016-1238-4. PubMed DOI

Zevallos VF, Raker V, Tenzer S, Jimenez-Calvente C, Ashfag-Khan M, Russel N, Pickert G, Schild H, Steinbrink G, Schuppan G. Nutritional wheat amylase-trypsin inhibitors promote intestinal inflammation via activation of myeloid cells. Gastroenterology. 2017;152:1100. doi: 10.1053/j.gastro.2016.12.006. PubMed DOI

Yan H, Martin SL, Bekele WA, Latta RG, Diederichsen A, Peng Y, Tinker NA. Genome size variation in the genus Avena. Genome. 2016;59:209–220. doi: 10.1139/gen-2015-0132. PubMed DOI

Gutierrez-Gonzalez JJ, Tu ZJ, Garvin DF. Analysis and annotation of the hexaploid oat seed transcriptome. BMC Genom. 2013;14:471. doi: 10.1186/1471-2164-14-471. PubMed DOI PMC

Li H. Minimap2: pairwise alignment for nucleotide sequences. Bioinformatics. 2018;34:3094–3100. doi: 10.1093/bioinformatics/bty191. PubMed DOI PMC

Li H, Handsaker B, Wysoker A, Fennell T, Ruan J, Homer N, Marth G, Abecasis G, Durbin R. 1000 genome project data processing subgroup: The sequence alignment/Map format and SAMtools. Bioinformatics. 2009;25:2078–2079. doi: 10.1093/bioinformatics/btp352. PubMed DOI PMC

Robinson JT, Thorvaldsdóttir H, Winckler W, Guttman M, Lander ES, Getz G, Mesirov JP. Integrative genomic viewer. Nat. Biotechnol. 2011;29:24–26. doi: 10.1038/nbt.1754. PubMed DOI PMC

Jukes TH, Cantor CR. Evolution of protein molecules. In: Munro HN, editor. Mammalian Protein Metabolism. Academic Press; 1969. pp. 21–132.

Tamura K, Peterson D, Peterson N, Stecher G, Nei M, Kumar S. MEGA5: molecular evolutionary genetics analysis using maximum likelihood, evolutionary distance, and maximum parsimony methods. Mol. Biol. Evol. 2011;28:2731–2739. doi: 10.1093/molbev/msr121. PubMed DOI PMC

Sollid LM, Qiao SW, Anderson RP, Gianfrani C, Koning F. Nomenclature and listing of celiac disease relevant gluten T-cell epitopes restricted by HLA-DQ molecules. Immunogenetics. 2012;64:455–460. doi: 10.1007/s00251-012-0599-z. PubMed DOI PMC

Anderson OD. The spectrum of major seed storage genes and proteins in oats (Avena sativa) PLoS ONE. 2014;9(7):e83569. doi: 10.1371/journal.pone.0083569. PubMed DOI PMC

Tanner G, Juhász A, Florides CG, Nye-Wood M, Békés F, Colgrave ML, Russel AK, Hardy MY, Tye-Din JA. Preparation and characterization of avenin-enriched oat protein by chill precipitation for feeding trials in celiac disease. Front. Nutr. 2019;6:162. doi: 10.3389/fnut.2019.00162. PubMed DOI PMC

Ahola HG, Sontag-Strohm TS, Schulman AH, Tanhuanpaa PO, Viitala S, Huang X. Immunochemical analysis of oat avenins in an oat cultivar and landrace collection. J. Cereal Sci. 2020;95:103053. doi: 10.1016/j.jcs.2020.103053. DOI

Ellis HJ, Pollock EL, Engel W, Fraser JS, Rosen-Bronson S, Wieser H, Ciclitira PJ. Investigation of the putative immunodominant T cell epitopes in celiac disease. Gut. 2003;52:212–217. doi: 10.1136/gut.52.2.212. PubMed DOI PMC

Shewry PR. Avenins” the prolamins of oats. In: Shewry PR, Casey R, editors. Seed Proteins. Springer; 1999. pp. 79–92.

Hardy MY, Tye-Din JA, Stewart JA, Schmnity F, Dudek NL, Hanchapola I, Purcell AW, Anderson RP. Ingestion of oats and barley in patients with celiac disease mobilizes cross-reactive T cells activated by avenin peptides and immune-dominant hordein peptides. J. Autoimmun. 2015;56:56–65. doi: 10.1016/j.jaut.2014.10.003. PubMed DOI

Tatham AS, Gilbert SM, Fido RJ, Shewry PR. Extraction, separation and purification of wheat gluten proteins and related proteins of barley, rye and oats. Methods Mol. Med. 2000;41:55–73. PubMed

Tan SY, Siow PC, Peh E, Henry CJ. Influence of rice, pea and oat proteins in attenuating glycemic response of sugar-sweetened beverages. Eur. J. Nutr. 2018;57:2795–2803. doi: 10.1007/s00394-017-1547-3. PubMed DOI

Junker Y, Zeissig S, Kim SJ, Barisani D, Wiesser H, Leffler DA, Zevallos V, Libermann TA, Dillon S, Freitag TL, Kelly CP, Schuppan DS. Wheat amylase trypsin inhibitors drive intestinal inflammation via activation of toll-like receptor 4. J. Exp. Med. 2012;209:2395–2408. doi: 10.1084/jem.20102660. PubMed DOI PMC

Wolfe D, Dudek S, Ritchie MD, Pendergrass SA. Visualizing genomic information across chromosomes with PhenoGram. BioData Mining. 2013;6:18. doi: 10.1186/1756-0381-6-18. PubMed DOI PMC