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  • Jefferson Adams
    Jefferson Adams

    Lactobacilli Degrade Amylase Trypsin Inhibitors and Reduce Intestinal Symptoms Caused by Immunogenic Wheat Proteins

      Amylase trypsin inhibitors influence wheat-induced intestinal symptoms in wild-type mice and increase inflammation to wheat proteins in genetically susceptible mice. Lactobacillus degrades and reduces the inflammatory effects of ATI.

    Caption: Image: CC--Army Medicine

    Celiac.com 03/20/2019 - Sensitivities to gluten are becoming more common. Patients with celiac disease have wheat-specific immune responses, but researchers have remained uncertain about the potential role of non-wheat proteins in triggering symptoms in celiac or gluten-sensitive patients.

    A team of researchers recently set out to assess the role of non-gluten proteins that may trigger symptoms in celiac or gluten-sensitive patients. Specifically, the team wanted to determine if lactobacillus degrades and/or reduces the inflammatory effects of amylase trypsin inhibitors (ATI).

    The research team included Alberto Caminero, Justin L. McCarville, Victor F. Zevallos, Marc Pigrau, Xuechen B. Yu, Jennifer Jury, Heather J. Galipeau, Alexandra V. Clarizio, Javier Casqueiro, Joseph A. Murray, Stephen M. Collins, Armin Alaedini, Premysl Bercik, Detlef Schuppan, and Elena F. Verdu.

    The researchers put mice on a gluten-free diet, with or without wheat amylase trypsin inhibitors (ATI), for one week. Mice included a control group of C57BL/6 mice, and groups of Myd88–/–, Ticam1–/–, and Il15–/– mice. The team then collected small intestine tissues and measured intestinal intraepithelial lymphocytes (IELs). They also looked at gut permeability and intestinal transit times.

    Control mice fed ATI for one week were fed daily with Lactobacillus strains with either high or low ATI-degrading capacity. The team sensitized NOD/DQ8 mice to gluten, and then fed them an ATI diet, a gluten-containing diet or a diet with ATI and gluten for two weeks. Mice were also treated with Lactobacillus strains that had high or low ATI-degrading capacity. The team took samples of intestinal tissues, and measured IELs, gene expression, gut permeability and intestinal microbiota profiles.

    Intestinal tissues from control mice show that ATI triggered an innate immune response by activating TLR4 signaling to MD2 and CD14, and impaired barrier function even in the absence of mucosal damage. 

    Gluten-sensitized mice carrying HLA-DQ8 showed increased intestinal inflammation in response to dietary gluten. The team found that lactobacillus degraded and reduced the inflammatory effects of ATI.

    In conclusion, amylase trypsin inhibitors influence gluten-induced intestinal symptoms in wild-type mice and increase inflammation to gluten in genetically susceptible mice. Lactobacillus degrades and reduces the inflammatory effects of ATI.

    Strategies to alter the gut microbiome, such as the ingestion of bacteria that can degrade and reduce  ATI, may be helpful for people with various wheat-sensitivities, including celiac disease.

    Read more at Gastroenterology

     

    The researchers are variously affiliated with the Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada; the Research Center for Immunotherapy, University Medical Center, Johannes Gutenberg University, Mainz, Germany; Institute of Translational Immunology, University Medical Center, Johannes Gutenberg University Mainz, Mainz, Germany; the Department of Medicine, Columbia University, New York, NY, USA; the Institute of Human Nutrition, Columbia University, New York, NY, USA; the Department of Microbiology. Universidad de Leon, Leon, Spain Division of Gastroenterology and Hepatology, Department of Immunology, Mayo Clinic College of Medicine, Rochester, Minnesota; the Research Center for Immunotherapy, University Medical Center, Johannes Gutenberg University, Mainz, Germany; Institute of Translational Immunology, University Medical Center, Johannes Gutenberg University Mainz, Mainz, Germany; and the Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.

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  • About Me

    Jefferson Adams earned his B.A. and M.F.A. at Arizona State University, and has authored more than 2,000 articles on celiac disease. His coursework includes studies in biology, anatomy, medicine, science, and advanced research, and scientific methods. He previously served as Health News Examiner for Examiner.com, and devised health and medical content for Sharecare.com. Jefferson has spoken about celiac disease to the media, including an appearance on the KQED radio show Forum, and is the editor of the book "Cereal Killers" by Scott Adams and Ron Hoggan, Ed.D.

  • Related Articles

    Jefferson Adams
    Celiac.com 02/01/2017 - More and more evidence shows a connection between gut inflammation and type 1 diabetes (T1D). A team of researchers recently set out to assess gut inflammatory profiles and microbiota in patients with T1D, and to compare them with healthy controls (CTRL) and with celiac disease patients as gut inflammatory disease controls.
    The research team included Silvia Pellegrini, Valeria Sordi, Andrea Mario Bolla, Diego Saita Roberto Ferrarese, Filippo Canducci, Massimo Clementi, Francesca Invernizzi, Alberto Mariani, Riccardo Bonfanti, Graziano Barera, Pier Alberto Testoni, Claudio Doglioni, Emanuele Bosi, and Lorenzo Piemonti. They are affiliated with the Diabetes Research Institute at the IRCCS San Raffaele Scientific Institute in Milan, Italy.
    The team evaluated inflammatory status and microbiome composition in biopsies of the duodenal mucosa from 19 patients with T1D, 19 with celiac disease, and 16 healthy control subjects, recruited at San Raffaele Scientific Institute, in Milan, Italy, between 2009 and 2015. They assessed inflammation by gene expression study and immunohistochemistry and used 16S rRNA gene sequencing to analyze microbiome composition.
    Compared to CTRL and celiac disease patients, the team found an increased expression of CCL13, CCL19, CCL22, CCR2, COX2, IL4R, CD68, PTX3, TNFα and VEGFA genes in T1D patients. The immunohistochemical analysis confirmed T1D specific inflammatory status was mainly marked by increased monocyte/macrophage lineage infiltration, compared to healthy and celiac disease control tissues.
    The T1D duodenal mucosal microbiome also proved to be different from the control groups. This was mainly marked by increased Firmicutes, and Firmicutes/Bacteroidetes ratio and a reduction in Proteobacteria and Bacteroidetes.
    The expression of genes specific for T1D inflammation was associated with the excess of specific bacteria in duodenum. This study shows that patients with T1D show specific abnormalities in gut inflammation and microbiota.
    Greater knowledge of the complex pathogenesis of T1D will likely provide new directions for therapies targeting the gut. Look for more studies in this area in the near future, as scientists look to nail down specific treatments to prevent gut inflammation.
    Source:
    The Journal of Clinical Endocrinology & Metabolism. DOI: https://doi.org/10.1210/jc.2016-3222

    Jefferson Adams
    Celiac.com 12/25/2017 - In the very near future, your personal microbiome may be the key to creating a customized treatment for celiac disease.
    That's because new advances in genome studies are promising to help create a customized, individual approach for treating numerous disorders, including celiac disease. Such individualized treatments may also help to reduce adverse events, and decrease health care costs.
    So far, a similar approach for optimizing preventive and therapeutic approaches in cancer using human genome sequencing has proven successful.
    Writing in the Mayo Clinic Proceedings, ad team of researches expounded on this approach. The research team included Purna C. Kashyap, Nicholas Chia, PhD, Heidi Nelson, MD, Eran Segal, PhD, and Eran Elinav, MD, PhD. They are variously affiliated with the Enteric Neuroscience Program, Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN; the Department of Surgery, Mayo Clinic, Rochester, MN; the Department of Computer Science at the Weizmann Institute of Science in Rehovot, Israel and with the Department of Immunology, at the Weizmann Institute of Science in Rehovot, Israel.
    Your personal microbiome is the sum total of all the microbes that reside within and upon you, along with all their genetic elements. Using genome sequencing allows doctors to design highly personal, highly focused treatments and therapeutic strategies.
    In their review for the Mayo Clinic Proceedings, the team highlights the importance of the microbiome in all aspects of human disease, including pathogenesis, phenotype, prognosis, and treatment response. The microbiome also plays a crucial role as a diagnostic and therapeutic biomarker.
    The team's report describes the role to be played by next-generation sequencing in helping to provide precision microbial identification of infectious diseases, and helping to elucidate the nature and function of microbial communities.
    Basically, as we further unlock the human genome, we can begin to better understand the role played by the myriad microbes that make up the human microbiome. As we unlock the role of various parts of the microbiome, look for major advances and refinements to diagnosing, treating, and even conquering conditions like celiac disease, and many others. And, with advances coming at breakneck speed, look for this to happen sooner, rather than later.
    Source:
    PlumX Metrics - mayoclinicproceedings.org

    Jefferson Adams
    Celiac.com 12/10/2018 - More and more people are eating gluten-free for non-medical reasons. These days, people with celiac disease make up a small percentage of overall gluten-free food sales. However, the effects of eliminating or reducing wheat, barley and rye ingredients from the diets of in healthy adults have not been well studied. A team of researchers recently set out to assess the effects of a gluten-free diet in healthy adults.
    To make their assessment, the researchers conducted a randomized, controlled, cross-over trial of 60 middle-aged Danish adults with no known diseases. The trial included two 8-week assessments comparing a low-gluten diet of 2 grams of gluten per day, and a high-gluten diet of 18 grams of gluten per day, separated by a washout period of at least six weeks with habitual diet including 12 grams of gluten per day. 
    Compared with a high-gluten diet, the data show that a low-gluten diet triggers slight changes in the intestinal microbiome, increases food and drink intake and postprandial hydrogen exhalation, and reduces self-reported bloating. The team’s data indicate that results of a low-gluten diet in non-celiac adults are likely triggered by qualitative changes in dietary fiber.
    Studies like this are important for understanding the effects of a gluten-free diet in both celiacs and non-celiacs alike. Better understanding of a gluten-free diet will help doctors, celiac patients, and healthy individuals to make better, more informed dietary decisions.
    Source:
    Nature Communications; volume 9, Article number: 4630 (2018)   
    The research team included Lea B. S. Hansen, Henrik M. Roager, Nadja B. Søndertoft, Rikke J. Gøbel, Mette Kristensen, Mireia Vallès-Colomer, Sara Vieira-Silva, Sabine Ibrügger, Mads V. Lind, Rasmus B. Mærkedahl, Martin I. Bahl, Mia L. Madsen, Jesper Havelund, Gwen Falony, Inge Tetens, Trine Nielsen, Kristine H. Allin, Henrik L. Frandsen, Bolette Hartmann, Jens Juul Holst, Morten H. Sparholt, Jesper Holck, Andreas Blennow, Janne Marie Moll, Anne S. Meyer, Camilla Hoppe, Jørgen H. Poulsen, Vera Carvalho, Domenico Sagnelli, Marlene D. Dalgaard, Anders F. Christensen, Magnus Christian Lydolph, Alastair B. Ross, Silas Villas-Bôas, Susanne Brix, Thomas Sicheritz-Pontén, Karsten Buschard, Allan Linneberg, Jüri J. Rumessen, Claus T. Ekstrøm, Christian Ritz, Karsten Kristiansen, H. Bjørn Nielsen, Henrik Vestergaard, Nils J. Færgeman, Jeroen Raes, Hanne Frøkiær, Torben Hansen, Lotte Lauritzen, Ramneek Gupta, Tine Rask Licht and Oluf Pedersen. 
    They are variously affiliated with the National Food Institute; the Department of Biotechnology and Biomedicine, Technical University of Denmark; the Department of Bio and Health Informatics; the Department of Chemical and Biochemical Engineering at the Technical University of Denmark in Lyngby, Denmark; the Department of Plant and Environmental Sciences; the Department of Nutrition, Exercise and Sports; the Department of Nutrition, Exercise and Sports; and the Department of Veterinary Disease Biology, Faculty of Science, University of Copenhagen in Frederiksberg, Denmark; the Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark; the Department of Clinical Biochemistry, Copenhagen University Hospital Hvidovre in Hvidovre, Denmark; the Department of Radiology, Bispebjerg Hospital in Copenhagen, Denmark; the Department of Autoimmunology & Biomarkers, Statens Serum Institut in Copenhagen, Denmark; the Department of Biology and Biological Engineering, Chalmers University of Technology in Gothenburg, Sweden; the School of Biological Sciences, The University of Auckland in Auckland, New Zealand; the Bartholin Institute, Rigshospitalet in Copenhagen, Denmark; the Research Centre for Prevention and Health, The Capital Region of Denmark in Frederiksberg, Denmark; the Research Unit and Department of Gastroenterology, Herlev and Gentofte Hospital, the Capital Region of Denmark in Herlev, Denmark; with Clinical-Microbiomics A/S in Copenhagen, Denmark; the Department of Microbiology and Immunology, KU Leuven–University of Leuven, Rega Institute; and VIB, Center for Microbiology in Leuven, Belgium; with Biostatistics, Department of Public Health, University of Copenhagen in Copenhagen, Denmark; the Laboratory of Genomics and Molecular Biomedicine, Department of Biology; the Novo Nordisk Foundation Center for Basic Metabolic Research; the Department of Radiology, Bispebjerg Hospital, Copenhagen, Denmark; and the Department of Biomedical Sciences; and the department of Biostatistics at the Department of Public Health at the University of Copenhagen, Copenhagen, Denmark.

    Plant Bioscience Ltd
    Celiac.com 02/15/2019 - Aiming for a wheat that is safe for people with coeliac disease and other gluten-sensitive individuals to consume, Professor Francisco Barro and colleagues of the CSIC Institute for Sustainable Agriculture in Cordoba, Spain have developed transgenic wheat lines in which the gliadin proteins (the gluten elements responsible for the damaging immune response of people with coeliac disease) have been strongly, and specifically, supressed.(1)
    Now, a study published in December 2018 in the journal Nutrients(2) has shown that fresh bread, made from the new wheat line, causes no negative response in non-coeliac gluten sensitive (NCGS) individuals when consumed regularly over several days. The bread was considered highly palatable by the trial participants. Moreover, in addition to the success in not triggering any acute gut symptoms, analysis of gut microbial populations demonstrated that the low-gliadin bread caused clear changes in the microbial profile consistent with a more beneficial population of natural bacteria, when compared to the profile present whilst consuming a gluten-free diet.
    The new wheat lines are being developed as an alternative option for people with gluten sensitivity by commercial partners of Plant Bioscience Limited, a UK-based technology transfer company, who have also patented the new wheat lines on behalf of CSIC.
    Prof. Barro said "This wheat opens up exciting new perspectives for NCGS patients; it's like following a gluten-free diet but with the aroma and taste of traditional wheat bread and favouring a much healthier microbiome."
    Professor Alastair Forbes, Clinical Professor in Medicine at the University of East Anglia, a leader in gastroenterology clinical research said; "This work is really encouraging news for the gluten sensitivity research community and the patients it serves. With no apparent drawbacks we now have a promising new wheat line in development that is non-toxic and promotes a healthier gut microbiome than the often-unpalatable gluten-free options hitherto available."
    Sarah Sleet, Coeliac UK chief executive said: "This is an exciting development showing real potential to develop a new bread from wheat, that may be suitable for people with coeliac
    disease. We’re not quite there yet, as this paper shows that bread from LGW is acceptable to people with gluten sensitivity but it has not completed testing in individuals with coeliac
    disease. We look forward to seeing the results of the ongoing tests in coeliac patients, who currently must follow a lifelong strict gluten-free diet to manage this serious autoimmune condition."
    For enquiries regarding the low-gliadin wheat, please contact Plant Bioscience Limited on telephone +44 (0)1603 45600, or via email info@pbltechnology.com.
    The full article can be read for free here: https://www.mdpi.com/2072-6643/10/12/1964 
    References:
    Effective shutdown in the expression of celiac disease-related wheat gliadin T-cell epitopes by RNA interference. Gil-Humanes J, Pistón F, Tollefsen S, Sollid LM, Barro F (2010). PNAS; 107(39): 17023-17028. The Dietary Intervention of Transgenic Low-Gliadin Wheat Bread in Patients with Non-Celiac Gluten Sensitivity (NCGS) Showed No Differences with Gluten Free Diet (GFD) but Provides Better Gut Microbiota Profile. Carmen Haro, Myriam Villatoro, Luis Vaquero, Jorge Pastor , María J. Giménez, Carmen V. Ozuna, Susana Sánchez-León, María D. García-Molina, Verónica Segura, Isabel Comino, Carolina Sousa, Santiago Vivas, Blanca B. Landa and Francisco Barro (2018). Nutrients; 10(12), 1964.

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