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Celiac.com 10/21/2024 - Wheat has been a staple in human diets for centuries, but for individuals with celiac disease and gluten sensitivities, consuming wheat can lead to serious health complications. The culprit? Gluten, particularly the gliadin fractions found in wheat, which trigger immune responses in those affected by celiac disease. A new study presents groundbreaking advancements in the field of gluten-free wheat production. Researchers have successfully used CRISPR/Cas9 technology to target and reduce gluten content by editing the genes responsible for the immunogenic gliadin proteins. Targeting Gliadin Genes with CRISPR/Cas9 The researchers in this study focused on two major groups of gliadin proteins: gamma (γ) and omega (ω) gliadins. These proteins are known to contain key epitopes that trigger adverse immune reactions in people with celiac disease. By designing eight specific single guide RNAs (sgRNAs), they were able to target and introduce mutations into these gliadin genes. Through the use of CRISPR/Cas9 multiplexing, a total of 59 wheat lines were produced, with 20 showing successful mutations in the target genes. This step marked a significant advance in reducing the gluten content of wheat. Massive Reduction in Gluten Content One of the most striking findings of the study was the 97.7% reduction in gluten content in the edited wheat lines. This was confirmed through various methods, including Reverse Phase High-Performance Liquid Chromatography (RP-HPLC) and monoclonal antibodies. The reduction was most noticeable in γ-gliadins and ω1,2-gliadins, while α-gliadins saw smaller decreases. These reductions make the modified wheat an incredibly promising candidate for gluten-free food products, although some limitations remain when it comes to fully eliminating all immunogenic components. Combining Multiple Mutations In addition to targeting γ- and ω-gliadins, the researchers took an extra step by crossing these modified lines with CRISPR/Cas9 lines that had already been edited for α-gliadins. This approach resulted in wheat lines with multiple mutations across different gliadin families, further enhancing the reduction of gluten content. By combining multiple edits, the research has moved closer to producing wheat that is significantly safer for people with celiac disease or gluten sensitivities. Quantifying the Success: R5 and G12 Monoclonal Antibody Tests To measure the gluten content in the edited wheat lines, the study used two monoclonal antibody tests, R5 and G12, which are standard in the food industry for detecting gluten in products. The R5 antibody is specifically raised against rye ω-secalins, which are similar to wheat ω-gliadins, while the G12 antibody targets α-gliadins. Both tests showed significant reductions in gluten, with some lines showing up to 97.7% less gluten. However, there were discrepancies between the two tests, with the G12 test showing slightly higher gluten content. This suggests that while the wheat lines are substantially gluten-reduced, there is still room for further refinement in achieving a completely gluten-free product. Future Implications: The Path to Non-Transgenic, Immune-Safe Wheat While previous efforts had been made to develop low-gluten wheat, this study is notable for demonstrating the feasibility of using CRISPR/Cas9 to edit multiple genes simultaneously in polyploid bread wheat. The result is a collection of wheat lines with drastically reduced levels of immunogenic proteins, moving closer to the goal of producing wheat that is safe for individuals with celiac disease. Importantly, these modified wheat lines are non-transgenic, meaning they do not contain foreign DNA, which may make them more acceptable to consumers and regulators. The next steps involve further testing, including stimulation assays using peripheral blood mononuclear cells (PBMCs) from individuals with celiac disease. These tests will help researchers identify which wheat lines cause the least immune response, with the ultimate goal of producing wheat that can be safely used in gluten-free products. A Step Toward Gluten-Free Wheat for Celiac Disease Patients For individuals with celiac disease, the promise of gluten-free wheat represents a potential game-changer. This study has made significant strides toward that goal by reducing the immunogenic gliadin proteins that cause adverse reactions. While further testing and development are necessary, the application of CRISPR/Cas9 technology in wheat breeding holds great promise for the future of gluten-free diets. The study does not specifically address the baking properties of the new wheat varieties with reduced gluten content. However, this is an essential consideration when developing gluten-free or gluten-reduced wheat. Gluten plays a critical role in baking, as it provides dough with its elasticity, structure, and ability to trap air during fermentation, leading to the light and airy texture of bread and other baked goods. When gluten is removed or reduced, it can significantly alter these properties, resulting in denser, less cohesive baked products. Therefore, it's crucial that any new gluten-free wheat varieties maintain similar baking characteristics, or alternative methods, such as adding binders like xanthan gum or psyllium husk, may be needed to replicate the qualities gluten imparts in baking. Balancing the reduction of immunogenic proteins with maintaining functional qualities is key to making the wheat practical for food production. This research is especially meaningful for those with celiac disease because it offers hope for a future where they can enjoy wheat-based foods without fear of triggering harmful immune responses. By creating wheat with drastically reduced gluten content, researchers are opening doors to new gluten-free food options that could improve the quality of life for millions of people worldwide. Read more at: academic.oup.com

Celiac.com 08/26/2024 - The study "Gluten is a Proinflammatory Inducer of Autoimmunity" explores the significant and diverse ways in which gluten, a protein found in many grains, affects human health. Although gluten is well-known for its role in celiac disease, its influence extends beyond this condition. The study reveals that gluten can trigger inflammation and contribute to the development of various autoimmune and chronic inflammatory diseases. This summary will break down the key findings of the study to explain how gluten affects the body and why this research matters, particularly for those with celiac disease. How Gluten Triggers Inflammation Gluten is composed of peptides that are difficult to digest, and when consumed, these peptides can cause harm by interacting with the immune system in the gut. Normally, the intestines act as a barrier, keeping harmful substances out while allowing nutrients to pass through. However, gluten disrupts this barrier by weakening the tight junctions between cells, making the gut more permeable. This increased permeability allows foreign molecules, including gluten peptides, to enter the bloodstream and reach various organs. Once in the bloodstream, these peptides can cause inflammation in distant parts of the body, not just in the intestines. The study also highlights that gluten can activate several inflammatory pathways in the body. One particular gluten component, gliadin, induces stress in the cells lining the gut, triggering a series of events that lead to a local inflammatory response. This response involves the activation of immune cells and the release of inflammatory molecules, which can cause further damage to the gut lining and contribute to chronic inflammation. Gluten and the Immune System Gluten is not just a trigger for inflammation; it also has a strong immunogenic effect, meaning it can stimulate the immune system in ways that lead to autoimmune diseases. In individuals with celiac disease, gluten peptides are modified by an enzyme called tissue transglutaminase (tTG), making them more likely to be recognized as harmful by the immune system. This recognition leads to the production of specific antibodies against gluten and tTG, which attack not only the gluten peptides but also the body’s own tissues, resulting in the symptoms of celiac disease. Interestingly, the study suggests that gluten can have similar effects even in people who do not have celiac disease. For example, gluten has been shown to elicit an immune response in individuals with non-celiac gluten sensitivity, a condition where people experience symptoms related to gluten intake despite not having the typical markers of celiac disease. This broad immunogenic potential of gluten underscores its role as a universal trigger of inflammation and autoimmunity. Systemic Distribution of Gluten Peptides One of the most concerning aspects of gluten's impact on health is its ability to affect organs far from the gut. After gluten peptides enter the bloodstream, they can travel to various parts of the body, where they may contribute to different health problems. The study provides evidence that gluten peptides can be found in tissues and organs such as the brain, thyroid, and other peripheral organs. In these locations, gluten can induce or exacerbate inflammatory and autoimmune processes. For instance, gluten has been implicated in neurological conditions, such as gluten ataxia, where it causes damage to the cerebellum, a part of the brain that controls coordination. This condition, like many other gluten-related disorders, is thought to arise from the immune system mistakenly attacking brain tissue in response to gluten peptides. Additionally, gluten peptides have been found in the thyroid gland, where they may play a role in autoimmune thyroid diseases like Hashimoto's thyroiditis. The Broader Implications of Gluten Consumption The findings of this study have broad implications, especially for individuals with celiac disease or other gluten-related disorders. The fact that gluten can trigger inflammation and contribute to autoimmune diseases even in people without celiac disease suggests that gluten might be a more widespread health concern than previously thought. The study also highlights the potential benefits of a gluten-free diet, not only for those with celiac disease but also for individuals with other chronic inflammatory or autoimmune conditions. For those with celiac disease, this research reinforces the importance of strict adherence to a gluten-free diet as the only effective way to prevent the harmful effects of gluten. For others, especially those with unexplained chronic inflammation or autoimmune diseases, it may be worth exploring the role of gluten in their diet and considering gluten withdrawal as a potential therapeutic strategy. Conclusion: Why This Study Matters This study sheds light on the multifaceted and far-reaching effects of gluten on the human body. It reveals that gluten is not just a concern for people with celiac disease but may also play a role in a wide range of other chronic inflammatory and autoimmune conditions. By understanding how gluten affects gut permeability, triggers immune responses, and spreads systemically to various organs, we gain valuable insights into its role in human health. For those with celiac disease, this research underscores the importance of a gluten-free diet, while also opening up new avenues for investigating gluten's impact on other conditions. This study could be a pivotal step in redefining our understanding of gluten and its potential risks for broader populations. Read more at: xiahepublishing.com