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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

Celiac.com 09/28/2018 - MIT researchers have found that intestinal stem cells removed from mice after fasting for 24 hours and grown in culture have twice the regenerative capacity of stem cells grown in culture from non-fasting mice. The study provides evidence that fasting induces a metabolic switch in the intestinal stem cells, switching from utilizing carbohydrates to burning fat. Switching these cells to fatty acid oxidation enhances their function significantly. The study also found that the beneficial effects of fasting can be reproduced by treating mice with a molecule that mimics the effects. Stem cell regeneration is dramatically improved by fasting in both young and older mice. Intestinal stem cells in humans lose their ability to regenerate as humans age, making it more difficult for older people to recover from gastrointestinal disease and disorders. Fasting and/or the use of drugs to mimic the regenerative effects of fasting on intestinal stem cells may, therefore, be useful to improve recovery from intestinal injury in older patients if the mice study findings are shown applicable to humans. This study brings to mind past research on the protein R-spondin1 which showed great potential in completely regenerating and restoring the intestinal lining. R-spondin1 was being developed as a drug by Nuvelo, Inc. of San Carlos, CA designated as NU206 in 2005. Despite early successful human safety clinical trials in 2008, research was shelved and the promising drug has continued to sit idle on the shelf for years. The patent for NU206 is now owned by ARCA Biopharma http://arcabio.com/ of Westminster, CO after a merger with Nuvelo, Inc. in 2009. Fasting to regenerate the intestinal lining is free and requires no FDA approvals (though physician supervision may be advised.) Fasting may provide other potential health benefits. A Yale study found that during dieting or fasting the compound beta-hydroxybutyrate is produced which inhibits the inflammatory response in several disorders including autoimmune diseases, type 2 diabetes, Alzheimer's disease, atherosclerosis, and autoinflammatory disorders. Fasting can also affect the activation of T cells. T cells are leukocytes, white blood cells. T cells are activated by antigens from pathogens presented to T cell receptors which initiates an immune response against the pathogens. In autoimmune disease, antigen presented to T cell receptors initiates an immune response which results in damage to the body itself. A Luxembourg Institute of Health study found that glutathione, important for metabolic waste disposal and detoxification, also acts as a switch which stimulates T cell energy metabolism while keeping T cells clear of metabolic wastes. Without glutathione, T cells remain inactive and sit in a hibernation state. T cell inactivity is undesirable for fighting off an infection, but, otherwise, keeping T cells inactive may ward off harmful effects of autoimmune disease. Fasting lowers the body's glutathione level as the body constantly consumes glutathione. In one 7-day fasting study involving healthy humans, a progressive decline in total glutathione concentration in leukocytes was found during seven days of starvation due to a decrease in free glutathione content. This study provides proof that fasting lowers glutathione levels in T cells. Hence, based on the Luxembourg study, fasting can reduce or stop the activity of T cells. Thus, fasting can be used to relieve the symptoms of autoimmune disease resulting from a T cell immune response, providing that the subject is otherwise infection free and has no condition requiring an active T cell response. Finally, as shown in a University of Southern California study, multiple fasting cycles lasting 2 to 4 days over a period of 6 months in both mice and humans work to rid the body of older and damaged white blood cells and trigger white blood stem cells to self-regenerate and fully repopulate the immune system with new white blood cells. Besides having applications to recovery from immune system damage caused by cancer chemotherapy toxicity, these immune system rejuvenation effects from fasting may have potential benefit applicable to treatment of autoimmune disorders. Sources: Fasting boosts stem cells' regenerative capacity. A drug treatment that mimics fasting can also provide the same benefit, study finds. Anne Trafton - MIT News Office May 3, 2018 http://news.mit.edu/2018/fasting-boosts-stem-cells-regenerative-capacity-0503 Fasting Activates Fatty Acid Oxidation to Enhance Intestinal Stem Cell Function during Homeostasis and Aging. Mihaylova MM, Cheng CW, Cao AQ, Tripathi S, Mana MD, Bauer-Rowe KE, Abu-Remaileh M, Clavain L, Erdemir A, Lewis CA, Freinkman E, Dickey AS, La Spada AR, Huang Y, Bell GW, Deshpande V, Carmeliet P, Katajisto P, Sabatini DM, Yilmaz ÖH. Cell Stem Cell. 2018 May 3;22(5):769-778.e4. doi: 10.1016/j.stem.2018.04.001. https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(18)30163-2 Mitogenic influence of human R-spondin1 on the intestinal epithelium. Kim KA, Kakitani M, Zhao J, Oshima T, Tang T, Binnerts M, Liu Y, Boyle B, Park E, Emtage P, Funk WD, Tomizuka K. Science. 2005 Aug 19;309(5738):1256-9. https://www.ncbi.nlm.nih.gov/pubmed/16109882 Nuvelo, Inc. Announces Positive Results from Phase 1 Clinical Trial of NU206 in Healthy Volunteers. Published: Dec 10, 2008 https://www.biospace.com/article/releases/nuvelo-inc-announces-positive-results-from-phase-1-clinical-trial-of-nu206-in-healthy-volunteers-/?keywords=nu206 Anti-inflammatory mechanism of dieting and fasting revealed. By Karen N. Peart February 16, 2015 https://news.yale.edu/2015/02/16/anti-inflammatory-mechanism-dieting-and-fasting-revealed Master detox molecule boosts immune defenses. Scientists discover an unknown immune mechanism. April 18, 2017 https://www.sciencedaily.com/releases/2017/04/170418120923.htm Glutathione Primes T Cell Metabolism for Inflammation. Mak TW, Grusdat M, Duncan GS, Dostert C, Nonnenmacher Y, Cox M, Binsfeld C, Hao Z, Brüstle A, Itsumi M, Jager C, Chen Y, Pinkenburg O, Camara B, Ollert M, Bindslev-Jensen C, Vasiliou V, Gorrini C, Lang PA, Lohoff M, Harris IS, Hiller K, Brenner D. Immunity. 2017 Apr 18;46(4):675-689. doi: 10.1016/j.immuni.2017.03.019. https://www.cell.com/immunity/fulltext/S1074-7613(17)30129-2 The effect of fasting on leukocyte and plasma glutathione and sulfur amino acid concentrations. Martensson J. Metabolism. 1986 Feb;35(2):118-21. https://www.ncbi.nlm.nih.gov/pubmed/3945186 Fasting triggers stem cell regeneration of damaged, old immune system BY Suzanne Wu - USC News June 5, 2014 https://news.usc.edu/63669/fasting-triggers-stem-cell-regeneration-of-damaged-old-immune-system/ Prolonged Fasting Reduces IGF-1/PKA to Promote Hematopoietic-Stem-Cell-Based Regeneration and Reverse Immunosuppression Chia-Wei Cheng, Gregor B. Adams, Laura Perin, Min Wei, Xiaoying Zhou, Ben S. Lam, Stefano Da Sacco, Mario Mirisola, David I. Quinn, Tanya B. Dorff, John J. Kopchick, Valter D. Longo Cell Stem Cell. 2014 Jun 5; 14(6): 810-823. https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(14)00151-9 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4102383/