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Celiac.com 12/05/2024 - Over the past five decades, the prevalence of celiac disease and gluten sensitivity has increased dramatically, leading researchers to investigate the underlying causes. While no single theory can explain the rise in gluten-related disorders, several supported by scientific research offer insights into why these conditions are becoming more common. Here are the most popular theories. 1. The Hygiene Hypothesis The hygiene hypothesis posits that modern improvements in hygiene have led to reduced exposure to pathogens, which in turn weakens the immune system’s ability to distinguish between harmful and harmless substances. This theory suggests that reduced contact with bacteria, viruses, and other microorganisms early in life leaves the immune system more prone to overreaction, including triggering autoimmune diseases like celiac disease. Several studies support this hypothesis, showing a correlation between increased hygiene practices in developed nations and the rise in autoimmune disorders. For example, a 2016 study found that children raised in environments with higher exposure to microbes, such as on farms or in large families, have lower rates of autoimmune conditions, including celiac disease . The theory suggests that early immune system training helps prevent overreaction to proteins like gluten later in life. 2. Changes in Wheat Cultivation Modern agricultural practices have altered wheat's genetic composition over the last century. Through selective breeding, wheat varieties have been developed that are more resilient, produce higher yields, and contain higher levels of gluten. Some researchers propose that these genetic changes have made modern wheat more likely to trigger gluten sensitivity or celiac disease. Although no genetically modified (GMO) wheat is commercially available, modern wheat varieties do contain higher levels of gluten, especially the types of gluten proteins most harmful to those with celiac disease. A study published in the American Journal of Clinical Nutrition in 2013 compared ancient wheat varieties like einkorn with modern wheat and found that older varieties contained less of the gluten peptides that trigger immune responses in celiac disease . 3. Increased Gluten Consumption in Modern Diets Another popular theory is that people today are consuming more gluten than previous generations. The proliferation of processed and convenience foods has led to gluten being added to a wide range of products beyond bread and pasta. As gluten is often used as a thickener, stabilizer, or flavor enhancer in processed foods, people may be unknowingly consuming more gluten, which could contribute to the rise in gluten-related disorders. A 2020 review in the journal Nutrients highlighted how the increased use of gluten in processed foods has raised overall gluten consumption. The study found that the modern diet includes gluten in unexpected places, such as sauces, soups, and even supplements. This increased exposure, combined with genetic predisposition, might lead to higher rates of gluten sensitivity and celiac disease. 4. Microbiome Alterations and Gut Health The human gut microbiome, which consists of trillions of bacteria and other microorganisms, plays a key role in regulating immune function and digestion. Changes in diet, widespread use of antibiotics, and other environmental factors have disrupted the balance of the gut microbiome in many individuals. Some researchers believe this disruption contributes to the increase in autoimmune diseases like celiac disease by weakening the immune system's ability to tolerate gluten. A growing body of research connects gut health and celiac disease. A 2021 study in Frontiers in Microbiology found that individuals with celiac disease often have distinct microbiomes compared to healthy individuals, with fewer beneficial bacteria and higher levels of pathogenic strains . This altered microbiome may influence the body's immune response to gluten, increasing the risk of developing celiac disease. 5. Early Introduction of Gluten to Infants There is ongoing debate about whether the timing of gluten introduction in infancy affects the development of celiac disease. Some researchers believe that introducing gluten too early or too late during a child’s development could increase the likelihood of triggering an autoimmune response. The "window of tolerance" hypothesis suggests that introducing gluten during a specific developmental window might help the immune system develop tolerance to it. A large study known as the PreventCD project, conducted in Europe, examined how the timing of gluten introduction affected celiac disease risk in genetically predisposed children. The results, published in The New England Journal of Medicine in 2014, indicated that neither early nor delayed gluten introduction significantly affected the risk of developing celiac disease, but other studies still explore whether a small window may exist. 6. Environmental Factors and Chemical Exposure Some researchers believe that increased exposure to environmental chemicals, pesticides, and additives may contribute to the rise in autoimmune conditions, including celiac disease. Glyphosate, a common herbicide used in modern agriculture, has been speculated to contribute to intestinal permeability (also known as leaky gut), which could increase the risk of developing autoimmune diseases like celiac disease. Although this theory is more controversial, some research suggests that environmental chemicals may play a role in the development of autoimmune diseases. A 2013 paper in Interdisciplinary Toxicology argued that glyphosate's effects on gut bacteria could impair digestion and immune regulation, potentially increasing the risk of gluten sensitivity . However, further research is needed to confirm the link between glyphosate and celiac disease. Conclusion The increased prevalence of celiac disease and gluten sensitivity is a complex issue with multiple contributing factors. Theories ranging from changes in wheat cultivation and higher gluten consumption to microbiome disruption and the hygiene hypothesis offer plausible explanations for why more people are developing gluten-related disorders today. While no single theory has been definitively proven, ongoing research continues to shed light on the factors driving this rise, helping scientists and healthcare providers better understand, diagnose, and treat these conditions. As awareness grows and research advances, a deeper understanding of the relationship between gluten and autoimmune disease will help individuals manage and prevent the development of celiac disease and gluten sensitivity in future generations. Watch the video version of this article:

Celiac.com 01/22/2018 - Celiac disease is marked by HLA-DQ2/8-restricted responses of CD4+ T cells to gluten from wheat, barley or rye. Currently, in order to properly diagnose celiac disease based on serology and duodenal histology doctors need patients to be on gluten-containing diets. This is a problem for many people, who prefer not to begin ingesting wheat again once they have adopted a gluten-free diet. This can present challenges for doctors attempting to diagnose celiac disease. It is known that HLA-DQ–gluten tetramers can be used to detect gluten-specific T cells in the blood of patients with celiac disease, even if they are on a gluten-free diet. The team set out to determine if an HLA-DQ–gluten tetramer-based assay can accurately identify patients with celiac disease. The research team included Vikas K. Sarna, Knut E.A. Lundin, Lars Mørkrid, Shuo-Wang Qiao, Ludvig M. Sollid, and Asbjørn Christophersen. They are variously affiliated with the Department of Immunology, Oslo University Hospital – Rikshospitalet, Norway; the KG Jebsen Coeliac Disease Research Centre, University of Oslo, Norway; the Department of Gastroenterology, Oslo University Hospital – Rikshospitalet, Norway; the Department of Medical Biochemistry, Oslo University Hospital – Rikshospitalet, Norway; and with the Centre for Immune Regulation, Oslo University Hospital – Rikshospitalet and University of Oslo, Norway. For their study, the team produced HLA-DQ–gluten tetramers and added them to peripheral blood mononuclear cells isolated from 143 HLA-DQ2.5+ subjects. There were a total of 62 subjects with celiac disease on a gluten-free diet, 19 subjects without celiac disease on a gluten-free diet due to perceived sensitivity, 10 subjects with celiac disease on a non-gluten-free diet, and 52 seemingly healthy individuals as control subjects. The team used flow cytometry to measure T cells that bound HLA-DQ–gluten tetramers. They then used researchers blinded to sample type, except for samples from subjects with celiac disease on a gluten-containing diet, to conduct laboratory tests and flow cytometry gating analyses. They also conducted analysis on test precision using samples from 10 subjects. They found that an HLA-DQ–gluten tetramer-based test that detects gluten-reactive T cells identifies patients with and without celiac disease with a high level of accuracy, regardless of whether patients are on a gluten-free diet. This test could conceivably allow celiac diagnosis while suspected patients are still on a gluten-free diet. The team notes that their results require a larger study for validation. Could reliable celiac diagnosis be done without making patients consume gluten? Will that become common? Stay tuned for more developments. Source: Gastrojournal.org

Celiac.com 10/22/2018 - A team of researchers recently set out to determine if there is any association between prenatal gluten exposure and offspring risk of type 1 diabetes in humans. The research team first designed a national prospective cohort study using the national health information registries in Denmark. They looked at data on pregnant Danish women enrolled into the Danish National Birth Cohort, between January 1996 and October 2002, and assessed maternal gluten intake, based on maternal consumption of gluten containing foods, as reported in a 360 item food frequency questionnaire at week 25 of pregnancy. The team gathered information on type 1 diabetes occurrence in the participants’ children, from 1 January 1996 to 31 May 2016 by linking to the Danish Registry of Childhood and Adolescent Diabetes. Overall, their study included data on 101,042 pregnancies in 91,745 women, of whom 70,188 filled out the food frequency questionnaire. Once they corrected the figures to account for multiple pregnancies, pregnancies ending in abortions, stillbirths, lack of information regarding the pregnancy, and pregnancies with implausibly high or low energy intake, they included 67,565 pregnancies and 63,529 women. Gluten intake averaged 13.0 grams per day, ranging from under 7 grams per day to more than 20 grams per day. There were 247 children with type 1 diabetes among the group, for an incidence rate of 0.37%, with an average follow-up of 15.6 years. Risk of type 1 diabetes in offspring increased proportionally with maternal gluten intake during pregnancy per 10 grams per day increase of gluten. Compared to women with the lowest gluten intake of under 7 grams per day, those with the highest gluten intake who consumed 20 or more grams a day had double the risk for type 1 diabetes development in their children. These numbers indicate that high gluten intake by mothers during pregnancy may increase the risk of their children developing type 1 diabetes. However, the team is calling for further study to confirm the findings, preferably in an intervention setting. Read more in BMJ 2018;362:k3547. doi: https://doi.org/10.1136/bmj.k3547 The research team included Julie C Antvorskov, assistant professor, Thorhallur I Halldorsson, professor in food science and nutrition, Knud Josefsen, senior researcher, Jannet Svensson, associate professor5, Charlotta Granström, statistician, Bart O Roep, professor, Trine H Olesen, research assistant, Laufey Hrolfsdottir, director, Karsten Buschard, professor, and Sjudur F Olsen, adjunct professor of nutrition. They are variously affiliated with the Bartholin Institute, Rigshospitalet in Copenhagen, Denmark; the Centre for Foetal Programming, Department of Epidemiology Research, Statens Serum Institute, Copenhagen, Denmark; the Unit for Nutrition Research, Landspitali University Hospital, Reykjavik, Iceland; the Faculty of Food Science and Nutrition, University of Iceland, Reykjavik, Iceland; the Copenhagen Diabetes Research Center (CPH-DIRECT), Department of Children and Adolescents, Copenhagen University Hospital Herlev, Herlev, Denmark; the Department of Diabetes Immunology, Diabetes and Metabolism Research Institute at the Beckman Diabetes Research Institute, City of Hope, Duarte, CA, USA; the Departments of Immunohematology and Blood Transfusion, Leiden University Medical Centre, Leiden, Netherlands; the Department of Education, Science, and Quality, Akureyri Hospital, Akureyri, Iceland; and the Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.