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The Differences between Gluten Sensitivity, Intestinal Biomarkers and Immune Biomarkers in Patients with First-Episode and Chronic Schizophrenia.
Dzikowski, M, Juchnowicz, D, Dzikowska, I, Rog, J, Próchnicki, M, Kozioł, M, Karakula-Juchnowicz, H
Journal of clinical medicine. 2020;9(11)
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Schizophrenia is a heterogeneous neuroimmune disorder with unknown mechanisms and aetiology. The goal of this clinical study was to compare and evaluate IgG and IgA sensitivity, inflammation, and gut integrity between 52 first episode Schizophrenia patients, 50 chronic Schizophrenia patients, and 60 healthy controls to explain whether there were any associations between these markers. Study results show that antigliadin IgG and IgA antibodies, as well as inflammatory markers such as hs-CRP and IL-6, were significantly higher in the first episodes of schizophrenia and chronic schizophrenia patients when compared to the healthy controls. Schizophrenia risk was 4-7% higher among those with elevated Antigliadin IgG and IgA antibody levels. In addition, smoking cigarettes has been shown to increase the risk of developing schizophrenia. Patients with chronic schizophrenia showed elevated levels of anti-Saccharomyces cerevisiae antibody and soluble CD14, indicating bacterial translocation and immune activation. To understand the mechanisms behind chronic Schizophrenia, which link inflammation, immune responses, and the gut-brain axis, further robust larger studies are necessary. The results of this study can be used by healthcare professionals to understand the relationship between intestinal permeability, inflammation, and food hypersensitivity.
Abstract
Schizophrenia is a heterogeneous disorder without a fully elucidated etiology and mechanisms. One likely explanation for the development of schizophrenia is low-grade inflammation, possibly caused by processes in the gastrointestinal tract related to gluten sensitivity. The aims of this study were to: (1) compare levels of markers of gluten sensitivity, inflammation and gut permeability, and (2) determine associations between gluten sensitivity, inflammation, and intestinal permeability in patients with first-episode/chronic (FS/CS) schizophrenia and healthy individuals (HC). The total sample comprised 162 individuals (52 FS; 50 CS, and 60 HC). The examination included clinical variables, nutritional assessment, and serum concentrations of: high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), soluble CD14 (sCD14), anti-Saccharomyces cerevisiae antibody (ASCA), antigliadin antibodies (AGA) IgA/IgG, antibodies against tissue transglutaminase 2 (anti-tTG) IgA, anti-deamidated gliadin peptides (anti-DGP) IgG. A significant difference between groups was found in sCD14, ASCA, hs-CRP, IL-6 and AGA IgA levels. AGA IgG/IgA levels were higher in the FS (11.54%; 30.77%) and CS (26%; 20%) groups compared to HC. The association between intestinal permeability and inflammation in the schizophrenic patients only was noted. The risk for developing schizophrenia was odds ratio (OR) = 4.35 (95% confidence interval (CI 1.23-15.39) for AGA IgA and 3.08 (95% CI 1.19-7.99) for positive AGA IgG. Inflammation and food hypersensitivity reactions initiated by increased intestinal permeability may contribute to the pathophysiology of schizophrenia. The immune response to gluten in FS differs from that found in CS.
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Non-Celiac Gluten Sensitivity Has Narrowed the Spectrum of Irritable Bowel Syndrome: A Double-Blind Randomized Placebo-Controlled Trial.
Shahbazkhani, B, Sadeghi, A, Malekzadeh, R, Khatavi, F, Etemadi, M, Kalantri, E, Rostami-Nejad, M, Rostami, K
Nutrients. 2015;7(6):4542-54
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Irritable bowel syndrome (IBS) is a condition that has a wide spectrum of symptoms and severity. This spectrum is narrowing due to advances in diagnostic tools and a better understanding of the etiologies of the disease. Recent studies have found that patients diagnosed with IBS may have specific food sensitivities that could relieve IBS-related symptoms. The aim of this trial was to evaluate the efficacy of a gluten-free diet on reducing the symptoms in patients with IBS. Clinical symptoms of 72 participants were measured for six weeks of either being on a gluten-free diet or gluten-containing diet. The findings of this study showed that a large number of patients with IBS are sensitive to gluten and their symptoms could be controlled with a gluten-free diet. Based on this study, the authors’ conclusions suggest that using the term of IBS can be misleading and that food sensitivities should be the first approach.
Abstract
Several studies have shown that a large number of patients who are fulfilling the criteria for irritable bowel syndrome (IBS) are sensitive to gluten. The aim of this study was to evaluate the effect of a gluten-free diet on gastrointestinal symptoms in patients with IBS. In this double-blind randomized, placebo-controlled trial, 148 IBS patients fulfilling the Rome III criteria were enrolled between 2011 and 2013. However, only 72 out of the 148 commenced on a gluten-free diet for up to six weeks and completed the study; clinical symptoms were recorded biweekly using a standard visual analogue scale (VAS). In the second stage after six weeks, patients whose symptoms improved to an acceptable level were randomly divided into two groups; patients either received packages containing powdered gluten (35 cases) or patients received placebo (gluten free powder) (37 cases). Overall, the symptomatic improvement was statistically different in the gluten-containing group compared with placebo group in 9 (25.7%), and 31 (83.8%) patients respectively (p < 0.001). A large number of patients labelled as irritable bowel syndrome are sensitive to gluten. Using the term of IBS can therefore be misleading and may deviate and postpone the application of an effective and well-targeted treatment strategy in gluten sensitive patients.
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Reintroduction of gluten following flour transamidation in adult celiac patients: a randomized, controlled clinical study.
Mazzarella, G, Salvati, VM, Iaquinto, G, Stefanile, R, Capobianco, F, Luongo, D, Bergamo, P, Maurano, F, Giardullo, N, Malamisura, B, et al
Clinical & developmental immunology. 2012;2012:329150
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A lifelong gluten-free diet (GFD) is mandatory for celiac disease (CD) but has poor compliance, justifying new strategies. Chemically altering the protein in wheat flour (transamidation of gliadin) reduces the reaction experienced in vitro in intestinal cells of CD patients. This randomized single blinded, controlled 90-day trial in 47 CD patients examines the safety of transamidated wheat flour compared to control. 35 patients received 50g a day of transamidated flour bread and 12 received 3.7g of non-transamidated flour bread. On day 15, 75% and 37% of patients in the control and experimental groups, respectively, showed clinical relapse whereas intestinal permeability was mainly altered in the control group. On day 90, 0 controls and 14 patients in the experimental group completed the challenge with no change to the autoantibody found in CD (Ttg) and other markers of CD. This study demonstrated that a protracted intake of gluten from chemically treated wheat flour was associated with a reduced number of relapses in challenged patients. Nevertheless, the enzyme reaction did not eradicate gluten activity in all CD patients examined. Whether an upgrade of the transamidation reaction might be instrumental in blocking other immune components involved in the mucosal lesion is under investigation.
Abstract
A lifelong gluten-free diet (GFD) is mandatory for celiac disease (CD) but has poor compliance, justifying novel strategies. We found that wheat flour transamidation inhibited IFN-γ secretion by intestinal T cells from CD patients. Herein, the primary endpoint was to evaluate the ability of transamidated gluten to maintain GFD CD patients in clinical remission. Secondary endpoints were efficacy in prevention of the inflammatory response and safety at the kidney level, where reaction products are metabolized. In a randomized single blinded, controlled 90-day trial, 47 GFD CD patients received 3.7 g/day of gluten from nontransamidated (12) or transamidated (35) flour. On day 15, 75% and 37% of patients in the control and experimental groups, respectively, showed clinical relapse (P = 0.04) whereas intestinal permeability was mainly altered in the control group (50% versus 20%, P = 0.06). On day 90, 0 controls and 14 patients in the experimental group completed the challenge with no variation of antitransglutaminase IgA (P = 0.63), Marsh-Oberhuber grading (P = 0.08), or intestinal IFN-γ mRNA (P > 0.05). Creatinine clearance did not vary after 90 days of treatment (P = 0.46). In conclusion, transamidated gluten reduced the number of clinical relapses in challenged patients with no changes of baseline values for serological/mucosal CD markers and an unaltered kidney function.