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A team of researchers has announced what they are calling a 'pivotal advance' regarding the differential influence of bifidobacteria and gram-negative bacteria on immune responses to inflammatory triggers in celiac disease. Their study provides strong evidence that various intestinal bacteria in celiac patients can influence inflammation, and that dietary probiotics and prebiotics can help improve the quality of life for patients with celiac and other associated diseases, such as type 1 diabetes and various autoimmune disorders. To conduct their study, they the team used cultures of human peripheral mononuclear cells (PBMCs) as in vitro models. This was possible because blood monocytes constantly replenish intestinal mucosal monocytes, and accurately represent an in vivo situation. To duplicate the intestinal environment surrounding celiac disease, researchers exposed cell cultures to Gram-negative bacteria and bifidobacteria they had isolated from celiac patients, both alone and in the presence of disease triggers. They then assessed the effects on surface marker expression and cytokine production by PBMCs. Gram-negative bacteria induced higher pro-inflammatory cytokines than did bifidobacteria. The Gram-negative bacteria also up-regulated expression of cell surface markers involved in inflammatory aspects of the disease, while bifidobacteria up-regulated the expression of anti-inflammatory cytokines. Research team still need to confirm the results in clinical trials on people, but the findings offer the first support for new treatment options that may change how celiac disease is treated and possibly prevented. In the same way the certain foods may contribute to poor health, notes Louis Montaner, D.V.M., M.Sc., D.Phil. Editor-in-Chief of the Journal of Leukocyte Biology, "others can have positive effects. For people with celiac disease, this opens a line of research into new therapies that may be as accessible as a grocer's shelf." SOURCE: Journal of Leukocyte Biology. 2010;87:765-778.
Celiac.com 06/14/2013 - A team of researchers recently conducted a controlled trial of gluten-free diet in patients with irritable bowel syndrome-diarrhea to gauge the effects on bowel frequency and intestinal function. Their goal was to determine whether a gluten-free diet might benefit patients with diarrhea-predominant irritable bowel syndrome (IBS-D). The team included M.I. Vazquez-Roque, M. Camilleri, T. Smyrk, J.A. Murray, E. Marietta, J. O'Neill, P. Carlson, J. Lamsam, D. Janzow, D. Eckert, D. Burton, A.R. Zinsmeister. They are variously affiliated with the Clinical Enteric Neuroscience Translational and Epidemiological Research at the Mayo Clinic in Rochester, Minnesota, and the Division of Gastroenterology and Hepatology at the Mayo Clinic in Jacksonville, Florida. The team designed a randomized controlled 4-week trial comparing the effects of a gluten-containing diet against gluten-free diet in 45 patients with IBS-D. They conducted genotype analysis for HLA-DQ2 and HLA-DQ8, and randomly placed twenty-two patients on the gluten-containing diet (11 HLA-DQ2/8 negative and 11 HLA-DQ2/8 positive) and 23 patients on the gluten-free diet (12 HLA-DQ2/8 negative and 11 HLA-DQ2/8 positive). They measured daily bowel function, small-bowel and colonic transit. They used lactulose and mannitol excretion to measure mucosal permeability, and peripheral blood mononuclear cells after exposure to gluten and rice to gauge cytokine production. The team collected rectosigmoid biopsy specimens from 28 patients, analyzed levels of messenger RNAs encoding tight junction proteins, and performed H&E staining and immunohistochemical analyses. They analyzed covariance models to compare data from the gluten-containing and gluten-free diet groups. They found that subjects on the gluten-containing diet had more bowel movements per day (P = .04); the gluten-containing diet had a greater effect on bowel movements per day of HLA-DQ2/8-positive than HLA-DQ2/8-negative patients (P = .019). They also found that the gluten-containing diet was associated with higher SB permeability, based on 0-2 h levels of mannitol and the ratio of lactulose to mannitol. They found that SB permeability to be greater in HLA-DQ2/8-positive than HLA-DQ2/8-negative patients (P = .018), and saw no significant differences in colonic permeability. Patients on the gluten-containing diet had a small decrease in expression of zonula occludens 1 in SB mucosa and significant decreases in expression of zonula occludens 1, claudin-1, and occludin in rectosigmoid mucosa. The effects of the gluten-containing diet on expression were substantially greater in HLA-DQ2/8-positive patients. Neither diet had any significant effects on transit or histology. Peripheral blood mononuclear cells produced higher levels of interleukin-10, granulocyte colony-stimulating factor, and transforming growth factor-α in response to gluten than rice, regardless of HLA genotype. The team's findings show that gluten alters bowel barrier functions in patients with IBS-D, especially in HLA-DQ2/8-positive patients, and that these aspects of IBS can be reversed with a gluten-free diet. Source: Gastroenterology. 2013 May;144(5):903-911.e3. doi: 10.1053/j.gastro.2013.01.049. Epub 2013 Jan 25.
Celiac.com 03/28/2012 - A clinical research team wanted to determine if adding ascorbate (vitamin C) to gliadin-stimulated biopsy culture could reduce the mucosal immune response to gliadin in people with celiac disease. The research team included D. Bernardo, B. Martínez-Abad, S. Vallejo-Diez, E. Montalvillo, V. Benito, B. Anta, L. Fernández-Salazar, A. Blanco-Quirós, J. A. Garrote, and E. Arranz. They are affiliated with the Mucosal Immunology Lab of the Department of Paediatrics & Immunology at Spain's Universidad de Valladolid-CSIC. Their quest was fueled by the understanding that the IL-15/NF-ÎºB axis plays a key role in celiac disease. Because ascorbate is known to inhibit effects on NF-ÎºB, the IL-15/NFÎºB axis looks like a good possible molecular target for reducing gliadin-induced inflammation in celiac disease. For their study, the team conducted in vitro gliadin challenges (100 Î¼g/ml) on duodenal biopsy explants from treated patients with celiac disease. Challenges were conducted with and without 20mM ascorbate. As an internal control, the team used an extra tissue explant in basal culture. The team then measured secretion levels of nitrites (3h), and IFNÎ³, TNFÎ±, IFNÎ±, IL-17, IL-13, and IL-6 (24h) on the supernatants. They measured IL-15 using western-blot on whole protein duodenal explants. When the team added ascorbate to in vitro culture gliadin-challenged biopsies, they found that the ascorbate blocked secretion of nitrites (p=0.013), IFNÎ³ (p=0.0207), TNFÎ± (p=0.0099), IFNÎ± (p=0.0375), and IL-6 (p=0.0036), as compared with samples from culture that received no ascorbate. They also found that the addition of ascorbate reduced cytokine secretion to levels even lower than those observed in basal cultures (IFNÎ³: p=0.0312; TNFÎ±: p=0.0312; IFNÎ±: p=0.0312; and IL-6: p=0.0078). Moreover, the gliadin-challenge triggered IL-15 production in biopsies from treated celiac disease patients, while IL-15 was completely blocked in the cultures that received ascorbate. Interestingly, ascorbate completely blocked IL-15 production even in the only treated celiac disease-patient who showed basal IL-15 production. From these results, the team concludes that ascorbate reduces the mucosal inflammatory response to gluten in an in vitro biopsy culture. As such, ascorbate might offer supplementary benefits in future celiac disease therapy. Source: Allergol Immunopathol (Madr). 2012 Jan-Feb;40(1):3-8.
Clin Immunol. 2004 Apr;111(1):108-18 According to German researchers, delaying the introduction of wheat and barley proteins could reduce the incidence of diabetes. The scientists looked at mice on diets that were modified according to protein source, and specifically looked at mice pups from female non-obese diabetic mice. Mice on lifelong wheat-free and barley-free diets (their protein source was poultry) had significantly reduced levels of diabetes (45% by age 32 weeks vs. 88% in control mice), and when they did develop diabetes, its onset was delayed. Interestingly the development of diabetes in these mice was not fully restored after adding wheat and barley proteins to their diets (58%). Further, insulin autoantibodies and insulitis scores were both reduced in the wheat and barley-free mice, and their intra-pancreatic IL-4 mRNA levels were increased. The researchers conclude: "These data support a link between dietary wheat and barley proteins and the development of autoimmune diabetes."