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How Xylitol and Gluten Change Human Gut Microbiota and Biofilm
Jefferson Adams posted an article in Latest Research
Celiac.com 04/18/2024 - Human gut microbiota contains many viruses, bacteria and fungi. Escherichia coli representatives are facultative anaerobic bacteria in the colon that play a crucial role in the metabolism of lactose, vitamin synthesis and immune system modulation. E. coli forms a biofilm on the epithelial cell surface of the intestine that can be modified by diet compounds, such as gluten, xylitol, lactose and probiotics. Researchers recently examined the impact of probiotic-derived Lactobacillus rhamnosus GG strain on non-pathogenic E. coli biofilm. They also also treated mono- and multi-species biofilm with gluten, xylitol and lactose. The research team included Joanna Kwiecińska-Piróg, Karolina Chomont, Dagmara Fydrych, Stawarz Julita, Tomasz Bogiel, Jana Przekwas, and Eugenia Gospodarek-Komkowska. They arę variously affiliated with the Microbiology Department, Pharmaceutical Faculty, Collegium Medicum in Bydgoszcz, University of Nicolaus Copernicus in Toruń in Bydgoszcz, Poland; and the Clinical Microbiology Division, Antoni Jurasz University Hospital no 1 in Bydgoszcz, Poland. Probiotics May be Helpful in Rebuilding Gut Microbiota After Broad Spectrum Antibiotic Therapy The researchers used 96-well plates to obtain biofilm growth. They stained the biofilm with crystal violet. To evaluate the type of interaction in mono- and multispecies biofilm, a new formula was introduced - biofilm interaction ratio index (BIRI). To describe the impact of nutrients on biofilm formation, they calculated the biofilm formation impact ratio (BFIR). The biofilms formed by both examined species are stronger than in monocultures. All the BIRI values were above 3.0. It was found that the monospecies biofilm of L. rhamnosus is strongly inhibited by gluten (84.5%), while the monospecies biofilm of E. coli is strongly inhibited by xylitol (85.5%). The mixed biofilm is inhibited by lactose (78.8%) and gluten (90.6%). The relations between bacteria in the mixed biofilm led to changes in biofilm formation by E. coli and L. rhamnosus GG. Study Highlights: • Combining E. coli and L. rhamnosus creates a stronger biofilm than when each bacterium is cultured alone. • Adding xylitol to the diet can decrease the formation of biofilms by E. coli bacteria. • Lactose and gluten are less effective than xylitol in reducing the formation of biofilms by E. coli bacteria. The results indicate tha t probiotics might be helpful in rebuilding the gut microbiota after broad spectrum antibiotic therapy, but only if gluten and lactose are excluded from diet. Graphic Abstract Read more at: Sciencedirect.com- 1 comment
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Celiac.com 09/06/2021 - Antibodies specific for peptides bound to human leukocyte antigen (HLA) molecules are valuable tools for studies of antigen presentation, and may have therapeutic potential. Human T cell receptor (TCR)–like antibodies that block immunodominant epitope recognition have potential as personalized medicine treatments for blunting gluten-activated T cell responses without compromising effector functions provided by other T cells. A team of researchers recently set out to generate human T cell receptor (TCR)–like antibodies toward the immunodominant signature gluten epitope DQ2.5-glia-α2 in celiac disease (CeD). Consuming gluten in food triggers the gastrointestinal symptoms of celiac disease in patients with CD4+ T cells specific for deamidated gluten peptides presented by disease-associated HLA-DQ class II MHC molecules. Frick and colleagues used phage display technology to look for TCR-like antibodies specific for an immunodominant gluten peptide bound by HLA-DQ2.5. By using phage display selection combined with secondary targeted engineering, the team was able to obtain highly specific antibodies with picomolar affinity. The team's antibody engineering improved affinity and binding stability, producing a superior TCR-like antibody that structurally mimicked the TCR interface with gluten peptide–MHC complexes. These TCR-like antibodies prevented triggering and expansion of gluten-responsive human CD4+ T cells both in vitro and in DQ2.5 transgenic mice. The binding geometry and interaction mode of the crystal structure of a Fab fragment of the lead antibody 3.C11 in complex with HLA-DQ2.5:DQ2.5-glia-α2 were very similar to prototypic TCRs specific for the same complex. Evaluation of celiac biopsy material confirmed celiac specificity and supports the idea that plentiful plasma cells present antigen in the inflamed gut of a celiac patient. Moreover, 3.C11 specifically blocked activation and proliferation of gluten-specific CD4+ T cells in vitro and in HLA-DQ2.5 humanized mice, suggesting that celiac disease mechanisms can potentially be blocked without weakening patient immunity. Read more in Science Immunology The research team included Rahel Frick, Lene S. Høydahl, Jan Petersen, M. Fleur du Pré, Shraddha Kumari, Grete Berntsen, Alisa E. Dewan, Jeliazko R. Jeliazkov, Kristin S. Gunnarsen, Terje Frigstad, Erik S. Vik, Carmen Llerena, Knut E.A. Lundin, Sheraz Yaqub, Jørgen Jahnsen, Jeffrey J. Gray, Jamie Rossjohn, Ludvig M. Sollid, Inger Sandlie and Geir Åge Løset. They are variously affiliated with the Centre for Immune Regulation and Department of Immunology, University of Oslo and Oslo University Hospital-Rikshospitalet, Oslo, Norway; the Centre for Immune Regulation and Department of Biosciences, University of Oslo, Oslo, Norway; the KG Jebsen Coeliac Disease Research Centre, University of Oslo, Oslo, Norway; the Infection and Immunity Program, Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia; the Australian Research Council Centre of Excellence for Advanced Molecular Imaging, Monash University, Clayton, Victoria, Australia; Nextera AS, Oslo, Norway; the Program in Molecular Biophysics, Johns Hopkins University, Baltimore, MD, USA; the Department of Gastroenterology, Oslo University Hospital-Rikshospitalet, Oslo, Norway; the Department of Gastrointestinal Surgery, Oslo University Hospital-Rikshospitalet, Oslo, Norway; the Institute of Clinical Medicine, University of Oslo, Oslo, Norway; the Department of Gastroenterology, Akershus University Hospital, Lørenskog, Norway; the Department of Chemical and Biomolecular Engineering and Institute of NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA; the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, USA; and the Institute of Infection and Immunity, Cardiff University School of Medicine, Heath Park, Cardiff, UK.
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Celiac.com 08/10/2015 - The presence of specific human leukocyte antigen-DQ2 and DQ8 seems to be necessary for celiac disease development, but its usefulness for screening is still uncertain. A research team recently set out to conduct a systematic review and meta-analysis of the diagnostic performance of human leukocyte antigen typing tests for celiac disease screening. The research team included A. Díaz-Redondo, J. Miranda-Bautista, J. García-Lledó, J.P. Gisbert, and L. Menchén. They are variously affiliated with the Hospital General Universitario Gregorio Marañón in Madrid, Spain, and with the Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Madrid, Spain. The team conducted a systematic review of published studies assessing accuracy of human leukocyte antigen DQ2 and DQ8 typing for the detection of celiac disease. They searched MEDLINE and EMBASE for the period running from 1st January 2004 until 31st December 2013 and used two independent researchers to carry out selection and classification of studies, data extraction and analysis. The team conducted meta-analysis that combined sensitivities, specificities and likelihood ratios of HLA-DQ2 and DQ8 for the diagnosis of celiac disease and ended up with six studies that included a total of 1303 people. The results showed pooled sensitivity at 98%, with 95% confidence interval: 97-99. Overall specificity was 45% (95% confidence interval: 41-48). Regarding specificity, studies were heterogeneous and a the team ran a subgroup analysis according to the type of population included. Overall negative likelihood ratio was 0.05 (0.03-0.09). Because it offers high sensitivity and low negative likelihood ratio, the team concludes that human leukocyte antigen-DQ2/DQ8 typing makes an appropriate test for ruling out celiac disease in the general population suffering related symptoms, and even more in at risk population. Source: Rev Esp Enferm Dig. 2015 Jul;107(7):423-429.
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Celiac.com 07/19/2016 - The world's first vaccine aimed at curing celiac disease is slated to begin full trials later this year, and residents of the Australian state of Victoria will be among the first humans to give it a try against celiac disease. The vaccine, called Nexvax2, was developed by Australian scientist Dr Bob Anderson, and is aimed at giving celiac patients a chance to overcome their immune reaction to the gluten found in products containing wheat, rye and barley. Nexvax2 aims to de-sensitise patients to three peptides contained in gluten that trigger a damaging reaction in their immune system. Previous trials on 150 patients from Melbourne, Perth, Adelaide, Brisbane and Auckland were aimed at finding a safe dosage rather than assessing its ability to beat celiac disease. Results from those favorable earlier trials were released in May, and Dr Anderson says that the larger phase II study, also being undertaken in the US and Europe, will assess how well the vaccine works against celiac disease. Dr Anderson first identified the peptides triggering coeliac disease and began developing the vaccine while working at Melbourne's Walter and Eliza Hall Institute, before travelling to Boston for six weeks as part of a sister city arrangement through the City of Melbourne, where he made contact with ImmusanT to further the discovery. This is certainly exciting news for people with celiac disease, many of whom may benefit from such treatment. Stay tuned for news on the progress of these trials. Source: dailysecrets.press
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Celiac.com 08/30/2017 - The human gut is home to a huge and diverse number of microorganisms that perform various biological roles. Disturbances in a healthy gut microbiome might help to trigger various inflammatory diseases, such as multiple sclerosis (MS). Human gut-derived commensal bacteria suppress CNS inflammatory and demyelinating disease. Can they improve the treatment of multiple Sclerosis (MS)? A team of researchers recently set out to evaluate evidence that gut commensals may be used to regulate a systemic immune response and may, therefore, have a possible role in treatment strategies for multiple Sclerosis. The research team included Ashutosh Mangalam, Shailesh K. Shahi, David Luckey, Melissa Karau, Eric Marietta, Ningling Luo, Rok Seon Choung, Josephine Ju, Ramakrishna Sompallae, Katherine Gibson-Corley, Robin Patel, Moses Rodriguez, Chella David, Veena Taneja, and Joseph Murray. In a recent article, the team reports on their identification of human gut-derived commensal bacteria, Prevotella histicola, which can suppress experimental autoimmune encephalomyelitis (EAE) in a human leukocyte antigen (HLA) class II transgenic mouse model. P. histicola suppresses disease through the modulation of systemic immune reactions. P. histicola challenge caused a reduction in pro-inflammatory Th1 and Th17 cells and an increase in CD4+FoxP3+ regulatory T cells, tolerogenic dendritic cells, and suppressive macrophages. This study indicates that gut commensals may regulate a systemic immune response, and so may have a role in future treatments for multiple Sclerosis, and possibly other autoimmune diseases such as celiac disease. Source: Cell.com. DOI: http://dx.doi.org/10.1016/j.celrep.2017.07.031
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Going Gluten Free as a Human Rights Issue
Yvonne Vissing Ph.D. posted an article in Summer 2016 Issue
Celiac.com 07/11/2016 - People with celiac disease know that going gluten free isn't a choice—it is a health necessity. It is also a human rights issue. Food and nutrition should be seen as a citizen's human and social right. People who fail to be attentive to the health needs of people with celiac disease may be violating their rights. Like many rights issues, people may not realize they've violated someone's rights by doing, or not doing, something. But when you are the one whose rights have been violated, you know. The violation is serious for you, even when others may be oblivious to the larger context of the violation. Thinking about being gluten-free in this context may be different from the way most people view celiac disease. But it is a point of view that is well worth considering. When you've got celiac disease and people aren't attentive to making sure you can eat gluten-free foods that are safely prepared and not contaminated, you can end up very sick in the short-run. The short-term effects may include symptoms such as gastrointestinal upset, migraines, fuzzy brain, sweats, and general malaise. As a fundamental right, what one eats should ensure people's access to a healthy, dignified and full life. People who have been "glutened" do not feel dignified as they writhe in pain, wrestle with fears of embarrassment, or modify their lifestyle and social schedules to accommodate the illness. In the long-run, if someone is continually exposed to gluten in foods, a variety of serious preventable health conditions may result. Unlike a peanut allergy that can directly kill you, exposure to gluten may result in morbidity and early mortality for people in an indirect fashion. Adhering to a gluten-free diet is of paramount importance to avoid health problems such as compromising one's weight and pubertal development, fertility, bone mineral density, and deficiencies of micro and macronutrients, not to mention the increased risk of developing malignancies, especially in the gastrointestinal system. Because the health effects of ingesting gluten for someone with celiac disease are less visible to those who don't experience them, they have been easier to ignore. Thanks to vocal advocates who now know that going gluten-free can save their lives, it is obvious that the lack of attention to making sure people can eat safely is a violation of their rights. Let's put the issue of gluten into a larger rights context. The United Nations Declaration of Human Rights (UDHR) was adopted in 1948 after World War II and it is the first global document that codified rights to which all human beings are inherently entitled. It contains a wide range of rights and is regarded as the foundation upon which other rights documents have been built. Its Article 25 states that "Everyone has the right to a standard of living adequate for the health and well-being of himself and of his family, including food, clothing, housing and medical care and necessary social services, and the right to security in the event of unemployment, sickness, disability, widowhood, old age or other lack of livelihood in circumstances beyond his control" (www.un.org/en/universal-declaration-human-rights/). The right to health and well-being are directly linked to food. Conditions like celiac disease, which are genetic in nature, are thus beyond one's control and necessary to be addressed through appropriate care and management. In another rights treaty document that pertains directly to the rights of children and youth, the UN Convention on the Rights of the Child (UNCRC) addresses in Article 3 that "In all actions concerning children….the best interests of the child shall be a primary consideration", that individuals responsible for them are required to ensure that they receive the services and protections they need, particularly in the areas of safety (and) health…". Article 24 "recognizes the right of the child to the enjoyment of the highest attainable standard of health and to facilities for the treatment of illness and rehabilitation of health. States Parties shall strive to ensure that no child is deprived of his or her right of access to such health care services". It goes on to emphasize the importance of disease prevention and primary health care "through the provision of adequate nutritious foods" (http://www.ohchr.org/en/professionalinterest/pages/crc.aspx). This implies that nutritious foods are linked with disease prevention and well-being, and making sure children (and adults) get the proper foods is in their best interests. If a child has celiac disease and the responsible adults are inattentive to making sure they can eat safely, they are in fact violating the child's rights. There are, then, international treaties that link food and nutrition directly with human rights. Juliana Nadal at the Department of Nutrition, Food Quality and Nutrition at the Federal University of Parana in Brazil reviews in her journal article, "The principle of human right to adequate food and celiac disease" (Demetra; 2013; 8(3); 411-423), a variety of ways that people who have celiac disease have their rights violated. Because celiac disease can be considered the most common food intolerance in the world, it is one that both individuals and social structures need to address as a mainstream issue. From how laws and consumer protections are designed at the macro level, to how food is made available and prepared at the micro level, rights of people with celiac disease hang in limbo. Some places and people are very attentive to their rights protections while others are not. Nadal contextualizes food and nutrition insecurity that afflicts individuals with celiac disease with specific regard to the principle of the Human Right to Adequate Food (HRAF). Diet is the single most secure treatment form for people with celiac disease. Managing one's diet enables one to control the magnitude of the disease. Laws, standards, practices and policies are necessary to secure HRAF for people with celiac disease. It is therefore important that the public be educated regarding this. By protecting individual fundamental human right to food availability in both quantity and quality, it reflects the value of society to protect the welfare of this group of people. Ultimately, rights protections promote and improve the health of the entire population. Rights violations may also be seen through the limited availability of products intended for celiac individuals in the market. Whether looking at gluten-free food as a local, state, regional, national or global issue, there are certain countries and areas that do not have access to the same quantity and variety of gluten-free foods as in other areas. Online shopping may make it easier for some people to access foods they need, but this option is not necessarily available to everyone. If foods essential for good diets are not accessible, this forces people to make dietary compromises that may not be in their best interest. Another area of rights violations for people who have to go gluten-free is the high cost of products. Simply put, gluten-free foods tend to cost more than other foods. People who have celiac disease have to use more of their scarce dollars to pay for food. This means there is less money available to pay for other necessities. Because gluten-free foods tend to be more expensive, this creates a social class barrier, especially for poor people or financially-strapped people with celiac disease. Poorer people will have their right to safe nutrition compromised because they can't afford the same foods as more affluent people who have celiac disease. The issue of gluten contamination contributes to a constant situation of food and nutritional insecurity to holders of this special dietary need. The celiac diet must be completely gluten-free, which allows people to have a life relatively free of major pathological complications. Maintaining a totally gluten-free diet is not an easy task because the violation of the diet may occur voluntarily or involuntarily, and range from incorrect information on food labels to the gluten contamination of processed products. Difficulties in the availability and access to food without gluten violates the principle of the human right to adequate food. The condition of being a celiac individual exposes one to permanent food and nutrition insecurity, which could cause loss of quality of life, socialization, and health of the individual, both in the short and long term. The problematic situation of food and nutritional insecurity that afflicts individuals with celiac disease can productively be addressed with regard to the principle of the human right to adequate food (HRAF) from the perspective of Food and Nutrition Security (FNS). It is important to know and recognize the real need of the people who live in some way under threat of food insecurity, how it impacts their health and lifestyle. Constructing, implementing and improving health policies in order to meet their needs is imperative to provide access to adequate food of nutritional quality. and to ensure that food, biological, social and cultural needs are achieved. By understanding food as a basic human right, it is easy to understand that the absence of safe foods that address the needs of celiac individuals represents a concrete case of a group of people who often may have their rights to adequate nutrition violated. As a result, many live in a state of food and nutrition insecurity. Food must be viewed as a constitutional right of all citizens, including those with special needs which require a special diet. -
Celiac.com 06/17/2013 - To investigate the prevalence of human leukocyte antigen (HLA) DQ2/8 alleles in Southern Italians with liver and gastrointestinal (GI) diseases outside of celiac disease, a team of researchers recently looked at human leukocyte antigen DQ2/8 prevalence in non-celiac patients with gastrointestinal diseases. The research team included Daniel DiGiacomo, Antonella Santonicola, Fabiana Zingone, Edoardo Troncone, Maria Cristina Caria, Patrizia Borgheresi, Gianpaolo Parrilli, and Carolina Ciacci. They are variously affiliated with the Gastrointestinal Unit of University Federico â…¡ in Naples, Italy, the Department of Medicine, Celiac Disease Center of Columbia University in New York, in the United States, The Celiac Center of Loreto Crispi Hospital in Naples, Italy, the Celiac Center, Gastrointestinal Unit in San Giovanni di Dio e Ruggi d’Aragona Hospital at the University of Salerno, and the Department of Medicine and Surgery, Campus di Baronissi at the University of Salerno Medical School in Baronissi, Italy. The team assessed HLA DQ2/8 status in 443 patients from three ambulatory gastroenterology clinics in Southern Italy. The clinics were located at the University of Federico â…¡ and Loreto Crispi Hospital in Naples, and Ruggi D’Aragona Hospital in Salerno. The team grouped patients according disease status for pre-post transplant liver disease, esophageal/gastric organic and functional diseases, irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD), along with DQ2/8 alleles, which correspond to a celiac disease genetic risk scale. They then compared allele frequencies in the test subjects with healthy Italian control subjects. Out of 443 subjects, the team found that 196 subjects (44.2%), tested positive for DQ2/8. The average age of DQ2/8 positive subjects was 56 years, and 42.6% were female. Overall, the team found that 86/188 (45.7%) patients with liver disease were HLA DQ2/8 positive, 39/73 (53.4%) with functional upper GI diseases and 19/41 (46.3%) with organic upper GI diseases were positive. Moreover, 38/105 (36.2%) patients with IBS and 14/36 (38.9%) with IBD were HLA DQ2/8 positive (P = 0.21). Additionally, people with functional upper GI diseases disorders had rates of DQ2/8 positivity that were nearly double those of healthy control subjects. Those with liver disease had rates of DQ2/8 positivity that were 1.3 percent higher than controls, though this rate is not statistically significant. People with IBS and IBD had a lower rates of DQ2/8 positivity compared to healthy controls. Compared to general population estimates, the percentage of individuals who were HLA DQ2/8 positive is higher in those with liver/upper functional GI disease and lower in IBS/IBD. Source: World J Gastroenterol 2013 April 28; 19(16): 2507-2513. ISSN 1007-9327 (print) ISSN 2219-2840 (online). doi:10.3748/wjg.v19.i16.2507
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Celiac disease is known to be triggered, at least in part, by environmental factors. These factors can even affect one identical twin and not the other and seem to have their greatest impact during infancy when gluten is first introduced to the diet. Gut flora makeup and vitamin D levels are 2 factors which differ in infants and could affect the development of the immune system in ways leading to celiac disease. Recent research has shown that gut Bifidobacterium levels are lower in both treated and untreated celiac disease patients. Bifidobacterium species have properties which are beneficial to the immune system such as increasing IL-10 secretion and decreasing intestinal permeability. But other microbiota species may also have important effects and benefits to the developing immune system. Scientists are only beginning to scratch the surface both in cataloging the microbiota species found in the gut and understanding how environmental factors, such as antibiotics, affect their makeup and, in turn, how the makeup of gut microbiota affects human health. A new article on Medscape.com discusses the current state of this research and is excellent reading: Gut Reaction: Environmental Effects on the Human Microbiota Melissa Lee Phillips Published on Medscape.com: 07/15/2009 http://www.medscape.com/viewarticle/705512_print It may be years before research fully understands how gut microbiota and vitamin D deficiency may be involved in triggering celiac disease. Both vitamin D and probiotic supplements (such as Bifidobacterium infantis) are cheap, readily available, and generally safe. There is much current research showing how important vitamin D is for overall health. Your infant's health is a matter of immediate concern and cannot wait 5 or 10 years for research to confirm whether such supplements can help prevent celiac disease. It would seem prudent to make use of these supplements now in both mother and infant during pregnancy, while breast-feeding, and prior to introducing gluten to your baby. Consult with your physician about how much is the right dose.
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Celiac.com 02/24/2010 - Proper clinical diagnosis of celiac diseasestill relies on confirmation of histological evidence of villousatrophy via biopsy. Getting a good sample can sometimes be tricky. Ifhistological sections are not optimally oriented, then diagnosis may bemore difficult. As a result, doctors can sometimes fail to confirm theproper diagnosis. A team of researchers recently set out tostudy the viability of confirming histological evidence of villousatrophy in real time, during upper gastrointestinal endoscopy, in liveduodenal mucosa of patients with celiac disease, using endocytoscopy, anovel diagnostic technique allowing in vivo real-time visualization ofmucosa under 450x magnification. The research team included T. Matysiak-Budnik, E. Coron1, J.-F. Mosnier, M. Le Rhun1, H. Inoue,and J.-P. Galmiche. They are associated variously with the Institutdes Maladies de l'Appareil Digestif - INSERM U913, CIC 04 et Serviced'Hépato-Gastroentérologie, Hôtel Dieu, CHU de Nantes, France, theService d'Anatomie Pathologique, E.A. Biometadys, CHU de Nantes,France, and the Digestive Disease Center, Showa University NorthernYokohama Hospital, Japan The team studied sixteen subjects withclinically proven celiac disease, together with seven controls subjectswith no celiac disease. They took endocytoscopic images from multipleareas and then made a blind comparison against standard histology. Endocytoscopy revealed three distinct patterns of in vivo histology. First,in all controls and eight celiac disease patients (n = 15),endocytoscopy revealed the presence of normal-appearing, long, thinvilli, lined with clearly distinguishable surface epithelial cells,considered to be normal duodenal mucosa. Second, in four celiacdisease patients, endocytoscopy revealed the presence of thick,shortened villi, reflecting partial villous atrophy. Finally,in four celiac disease patients, endocytoscopy revealed the totalabsence of villi, along with the presence of enlarged crypt orifices,reflecting total villous atrophy. The team found solid agreement between endocytoscopy and standard histology in all 16 patients with celiac disease. Fromtheir results, they conclude that endocytoscopy permits live,real-time, noninvasive imaging and assessment of villous architecture,and looks to be a promising method for in vivo evaluation of duodenalmucosa in celiac disease. Source: Endoscopy: DOI: 10.1055/s-0029-12438
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A team of researchers with the Department of Medicine at the University Erlangen-Nuernberg in Germany recently set out to examine the role of the innate immune system in celiac disease. The team included Maryam Rakhimova, Birgit Esslinger, Anja Schulze-Krebs, Eckhart G. Hahn, Detlef Schuppan and Walburga Dieterich. The researchers matured dendritic cells taken from venous blood of patients with both active and with treated celiac disease, along with DQ2–DQ8-positive or negative control subjects. They treated the dendritic cells with a peptic–tryptic digest of gliadin (500 μg/ml) and assessed activation by means of fluorescent-activated cell sorting analysis, cytokine secretion, and the cells' ability to trigger T cell proliferation. The team noted that gliadin up-regulated interleukin (IL)-6, IL-8, and IL-12 (p40) secretion in dendritic cells and triggered clear expression of the maturation markers human leukocyte antigen (HLA)-DR, CD25, CD83, and CD86 in all test subjects, without regard to their genotype or the presence of disease; whereas the digest of bovine serum albumin had no effect. However, gliadin-stimulated dendritic cells from patients with active celiac disease showed greater stimulation of autologous T cells compared to the other groups. The team concluded that further research should be aimed at identifying the mechanisms that control inflammation in healthy individuals. Source: J Clin Immunol, Volume 29, Number 1, January, 2009
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Celiac.com 10/28/2005 - Alba Therapeutics Corporation (Alba) today announced successful completion of its first Phase I trial for the drug candidate AT-1001, and that the FDA has granted Fast Track designation to AT-1001 for treatment of celiac disease. We are pleased to have concluded our first human study of oral AT-1001 and delighted that the FDA has granted fast track status to AT-1001. These two events are important additional milestones in our efforts to help those suffering from celiac disease, a disease for which there is no effective treatment, said Blake Paterson, MD, President and CEO of Alba. Alba plans to begin a proof of concept study demonstrating efficacy of AT-1001 in celiac patients within the next few months. Fast track process is designed to facilitate development and expedite the review of new drugs with the potential to address significant unmet medical needs for the treatment of serious or life-threatening conditions. Potential fast track benefits include FDA input into development, submitting new drug applications in sections rather than all at once and the option of requesting Accelerated Approval. About Celiac Disease Celiac disease is a T-cell mediated auto-immune disease that occurs in genetically susceptible individuals and is characterized by small intestinal inflammation, injury and intolerance to gluten. Gluten is a mixture of proteins found in common food grains such as wheat, rye and barley. According to the NIH, celiac disease affects approximately 3 million Americans, although the diagnosis is rarely made. The only treatment for celiac disease is complete elimination of gluten from the diet, which results in remission for some patients. About Zonulin Zonulin is an endogenous signaling protein that transiently and reversibly opens the tight junctions (tj) between the cells of epithelial and endothelial tissues such as the intestinal mucosa, blood brain barrier and pulmonary epithelia. Discovered by Alba co-founder Dr. Alessio Fasano, zonulin appears to be involved in many disease states in which leakage occurs via paracellular transport across epithelial and endothelial tight junctions (tj), and thus may play an important potential role in the treatment of auto-immune diseases. About Alba Alba Therapeutics Corporation is a privately held biopharmaceutical company based in Baltimore, Maryland. Alba is dedicated to commercializing disease-modifying therapeutics and drug delivery adjuvants based on the zonulin pathway. Albas lead molecule, AT-1001, is targeted towards the treatment of Celiac Disease and Type 1 Diabetes. Contact: Dr. Blake Paterson Alba Therapeutics Corporation 410-522-8708
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Celiac.com 06/25/2003 - Below is an abstract of yet another study that supports the use of human anti-tTG type IgA serological tests to accurately diagnose celiac disease: Alimentary Pharmacology & Therapeutics Volume 17 Issue 11 Page 1415 - June 2003 Antibodies to human recombinant tissue transglutaminase may detect coeliac disease patients undiagnosed by endomysial antibodies N. Tesei*, E. Sugai*, H. Vázquez*, E. Smecuol*, S. Niveloni*, R. Mazure*, M. L. Moreno*, J. C. Gomez, E. Mauriño* & J. C. Bai* Background: The screening and diagnosis of coeliac disease have been simplified by the advent of new serological tools. Aim: To assess the clinical utility of a newly developed kit for antibodies to human recombinant tissue transglutaminase (hu-anti-tTG) in a large population of patients undergoing intestinal biopsy for suspected intestinal disorders. Methods: We evaluated 426 serum samples from consecutive adult patients (250 from untreated coeliac disease patients and 176 from individuals in whom a diagnosis of coeliac disease had been excluded), obtained at the time of intestinal biopsy. Samples were tested for immunoglobulin A (IgA) hu-anti-tTG by enzyme-linked immunoabsorbent assay, IgA endomysial antibodies (EmA) by indirect immunofluorescence and IgA and IgG antigliadin antibodies by enzyme-linked immunoabsorbent assay. A sub-group of samples was also assessed for a guinea-pig-based anti-tissue transglutaminase. Results: According to the cut-off for hu-anti-tTG, the sensitivity, specificity and positive and negative predictive values were 91%, 96%, 97% and 87%, respectively. Simultaneous determination of EmA showed values of 86%, 100%, 100% and 83% for the same parameters. Although 19 coeliac disease patients (7.6%) were negative for EmA and hu-anti-tTG, both tests rendered superior statistical values to antigliadin antibody tests. At diagnosis, IgA deficiency was detected in 11 patients, but both assays were able to detect samples with mild to moderate deficiency. The comparison of hu-anti-tTG with EmA showed excellent concordance between the tests ( statistic, 0.85). Discordance was observed in 20 samples from coeliac disease patients (8%) and in nine samples from controls (5%). Fifteen samples had an EmA-negative but hu-anti-tTG-positive serology, and five showed the converse pattern. Comparison of human recombinant and guinea-pig tests showed concordant results in 96% of cases. Conclusions: The quantitative determination of hu-anti-tTG type IgA using a commercial enzyme-linked immunoabsorbent assay kit was highly sensitive and specific for the detection of coeliac disease. Our results in a large population of patients with a clinical condition suggestive of the disorder demonstrated that the test can be used to detect a substantial number of patients otherwise unrecognized by IgA EmA.
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Dietary Proteins in Human Milk
Scott Adams posted an article in Casein / Cows Milk Intolerance and Celiac Disease
Proteins ingested by mother can appear in the breast milk. There is well known disease in breast fed babies called eosinophilic colitis, which causes eosinophilic infiltration in the large intestine of the babies and clinically presents as rectal bleeding. The therapy is very simple: the mother stops ingesting cow milk and cow milk products and the babies do not have bleeding and they are completely well. Based on this clinical syndrome, the same possibility exists for the presence of gluten peptides in Human milk. Studies on this have been done by Dr. Reichelt.
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