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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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Multifactorial Etiology of Anemia in Celiac Disease and Effect of Gluten-Free Diet: A Comprehensive Review.
Martín-Masot, R, Nestares, MT, Diaz-Castro, J, López-Aliaga, I, Alférez, MJM, Moreno-Fernandez, J, Maldonado, J
Nutrients. 2019;11(11)
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Anaemia is a common clinical expression of Celiac Disease (CD) alongside vitamin B12, iron and folate deficiencies. This review looks at the latest evidence and effects of a gluten free diet, the mainstay of treatment for CD. Typically, symptoms subside whilst adhering to a GF diet however in 20% of people anaemia and nutrient deficiencies can persist. Some of this is attributed to lack of adherence to the diet, oftentimes accidental given the wide range of foods containing gluten. This in turn leads to further damage of the intestine and can be difficult to detect and monitor effectively. Inflammation of the gastrointestinal tract, and malabsorption, are the main reasons for nutrient deficiencies leading to anaemia in CD. Iron is a critical nutrient which can easily be affected by damage to the intestinal villi, common in CD, and over time lead to iron deficiency anaemia as the body is unable to absorb dietary iron and the body’s iron stores are depleted. Likewise, absorption of vitamins B12 and B9 (folate) are also impaired by damaged villi and vitamin B12 is further affected by small intestine injuries including decreased gastric acid production, bacterial overgrowth and reduced intrinsic factor efficiency. Deficiencies of these two nutrients can lead to macrocytic anaemia with low blood cell volumes. Overall a gluten free diet is shown to reduce symptoms of CD in a matter of weeks. The more patients adhere to the diet, the more the risk of nutrient deficiencies and anaemia reduces.
Abstract
Celiac disease (CD) is a multisystemic disorder with different clinical expressions, from malabsorption with diarrhea, anemia, and nutritional compromise to extraintestinal manifestations. Anemia might be the only clinical expression of the disease, and iron deficiency anemia is considered one of the most frequent extraintestinal clinical manifestations of CD. Therefore, CD should be suspected in the presence of anemia without a known etiology. Assessment of tissue anti-transglutaminase and anti-endomysial antibodies are indicated in these cases and, if positive, digestive endoscopy and intestinal biopsy should be performed. Anemia in CD has a multifactorial pathogenesis and, although it is frequently a consequence of iron deficiency, it can be caused by deficiencies of folate or vitamin B12, or by blood loss or by its association with inflammatory bowel disease (IBD) or other associated diseases. The association between CD and IBD should be considered during anemia treatment in patients with IBD, because the similarity of symptoms could delay the diagnosis. Vitamin B12 deficiency is common in CD and may be responsible for anemia and peripheral myeloneuropathy. Folate deficiency is a well-known cause of anemia in adults, but there is little information in children with CD; it is still unknown if anemia is a symptom of the most typical CD in adult patients either by predisposition due to the fact of age or because biochemical and clinical manifestations take longer to appear.
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Neurological Manifestations of Neuropathy and Ataxia in Celiac Disease: A Systematic Review.
Mearns, ES, Taylor, A, Thomas Craig, KJ, Puglielli, S, Leffler, DA, Sanders, DS, Lebwohl, B, Hadjivassiliou, M
Nutrients. 2019;11(2)
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Coeliac disease (CD) is a chronic, immune-mediated enteropathy in which dietary gluten triggers an inflammatory reaction of the small intestine in genetically predisposed individuals. The clinical presentation of the disease varies broadly and may include both intestinal symptoms and extra-intestinal manifestations, including iron-deficiency anaemia, osteoporosis, dermatitis herpetiformis, and neurological disorders, such as peripheral neuropathies and ataxia (a condition that affects co-ordination, balance and speech). Many patients who present with neurological manifestations of CD have no gastrointestinal symptoms, commonly leading to a delay in diagnosis. The aim of this systematic review was to assess the prevalence of peripheral neuropathies and gluten ataxia. Nine studies on gluten ataxia and 13 on gluten neuropathy were included in this review. The prevalence of both, neuropathy and ataxia, in the general population is very low, but this risk is increased in patients with CD. Estimates of the prevalence of neuropathy in CD patients ranged from 0% to 39%, with an increased risk in older and female patients. Prevalence of gluten ataxia varied from 0% to 6%. Symptoms of gluten neuropathy improve when patients with CD follow a gluten free diet (GFD), whilst the benefits of a GFD for ataxia vary between studies, possibly due to differences in study design. The authors note that this review primarily concentrated on patients with CD (i.e. those with evidence of enteropathy). However, neurological manifestations may exist in the presence of anti-gliadin antibodies alone (gluten sensitivity without evidence of enteropathy), and such patients benefit equally from a GFD. The authors conclude that patients with CD have an increased risk of gluten ataxia and gluten neuropathy, and that clinicians should check for gluten sensitivity in patients with ataxia and neuropathy of unknown origin.
Abstract
Celiac disease (CD) is an immune-mediated gastrointestinal disorder driven by innate and adaptive immune responses to gluten. Patients with CD are at an increased risk of several neurological manifestations, frequently peripheral neuropathy and gluten ataxia. A systematic literature review of the most commonly reported neurological manifestations (neuropathy and ataxia) associated with CD was performed. MEDLINE, Embase, the Cochrane Library, and conference proceedings were systematically searched from January 2007 through September 2018. Included studies evaluated patients with CD with at least one neurological manifestation of interest and reported prevalence, and/or incidence, and/or clinical outcomes. Sixteen studies were included describing the risk of gluten neuropathy and/or gluten ataxia in patients with CD. Gluten neuropathy was a neurological manifestation in CD (up to 39%) in 13 studies. Nine studies reported a lower risk and/or prevalence of gluten ataxia with a range of 0%⁻6%. Adherence to a gluten-free diet appeared to improve symptoms of both neuropathy and ataxia. The prevalence of gluten neuropathy and gluten ataxia in patients with CD varied in reported studies, but the increased risk supports the need for physicians to consider CD in patients with ataxia and neurological manifestations of unknown etiology.
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Prevalence of osteoporosis and osteopenia in men and premenopausal women with celiac disease: a systematic review.
Ganji, R, Moghbeli, M, Sadeghi, R, Bayat, G, Ganji, A
Nutrition journal. 2019;18(1):9
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Coeliac disease (CD) is an autoimmune disorder and is known to be associated with a decrease in bone mineral density (BMD). Findings suggest 40-70% of patients with coeliac disease (CD) have low BMD, however this prevalence has been reported without considering confounding variables, such as age, menopause status, lifestyle factors and co-morbidities. The purpose of this review was to show the prevalence of osteoporosis and osteopenia in men and premenopausal women with coeliac disease (CD). This systematic review included 19 studies representing 563 subjects. Based on the current literature the pooled prevalence of osteoporosis was 14.4% and osteopenia was 39.6%. According to these results, the authors conclude bone loss is more prevalent in those with CD however larger case-controlled studies are required to adjust for confounding factors.
Abstract
BACKGROUND Celiac disease (CD) is known as a reason of metabolic osteopathy. Progression of non-invasive methods such as bone densitometry has shown that an important ratio of CD cases is faced with impaired bone mass and such cases are prone to bone fractures. Variety of low bone mineral density in CD is probably because of ignored confounding factors such as age, menopause, and drug. The aim of our study was to systematically review the osteoporosis and osteopenia incidences among premenopausal females and males with CD. METHODS This systematic review was done based on preferred reporting items for systematic reviews (PRISMA) guidelines. PubMed and Scopus and Cochran databases were searched according to the relevant medical subject headings (MeSH) of CD and bone mineral density until 2018. Prevalence of osteopenia and osteoporosis were used as effect size for meta-analysis. Cochrane Q (p < 0.05) and I2 index were presented to reveal the heterogeneity. RESULTS 54 eligible full text reviews were included and nineteen selected for data extraction. Eleven articles didn't have our inclusion criteria and had ignored confounding factors like age and menopause, and we excluded; data extraction was done in eight studies. A total of 563 premenopausal women and men who were from, UK, Brazil, India, Hungary, and Poland were included. The pooled prevalence of osteoporosis was 14.4% [95%CI: 9-20.5%] (Cochrane Q = 7.889, p = 0.96, I2 = 49.29%), and osteopenia was 39.6% [31.1-48.8%] (Cochrane Q = 14.24, p = 0.07, I2 = 71.92%), respectively. CONCLUSION Our findings suggest that bone loss is more prevalent in celiac disease and can be associated with increased risk of fracture. However, but results are pooled prevalence and we need more case -control studies with more sample size and consideration of confounding factors.
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Mood Disorders and Gluten: It's Not All in Your Mind! A Systematic Review with Meta-Analysis.
Busby, E, Bold, J, Fellows, L, Rostami, K
Nutrients. 2018;10(11)
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Gluten is a protein found in grains such as wheat, barley and rye. For some people, gluten can cause serious health issues such as coeliac disease (CD). A growing body of research suggests that mood symptoms are associated with gluten-related disorders. The objective of this systematic review and meta-analysis was to establish whether a relationship exists between mood and gluten consumption. 13 studies were included in the meta-analysis. A gluten-free diet (GFD) significantly reduced depressive symptoms in 953 participants overall. Subgroup analyses revealed no difference in effect on mood between those with and without diagnosed CD or between those with a genetic predisposition to CD. In patients diagnosed with classical CD, a GFD resulted in a statistically significant reduction in mood symptoms, whereas the effect for silent CD patients was not significant. The authors concluded that gluten elimination may represent an effective treatment strategy for mood disorders in individuals with gluten-related disorders. Future studies should focus on gluten and mood in participants without a gut-related disorder, for example, in a population sample with depression. Finally, the level of support available to help a patient in maintaining a GFD diet over time should be carefully considered when recommending a GFD in practice.
Abstract
Gluten elimination may represent an effective treatment strategy for mood disorders in individuals with gluten-related disorders. However, the directionality of the relationship remains unclear. We performed a systematic review of prospective studies for effects of gluten on mood symptoms in patients with or without gluten-related disorders. Six electronic databases (CINAHL, PsycINFO, Medline, Web of Science, Scopus and Cochrane Library) were searched, from inception to 8 August 2018, for prospective studies published in English. Meta-analyses with random-effects were performed. Three randomised-controlled trials and 10 longitudinal studies comprising 1139 participants fit the inclusion criteria. A gluten-free diet (GFD) significantly improved pooled depressive symptom scores in GFD-treated patients (Standardised Mean Difference (SMD) -0.37, 95% confidence interval (CI) -0.55 to -0.20; p < 0.0001), with no difference in mean scores between patients and healthy controls after one year (SMD 0.01, 95% CI -0.18 to 0.20, p = 0.94). There was a tendency towards worsening symptoms for non-coeliac gluten sensitive patients during a blinded gluten challenge vs. placebo (SMD 0.21, 95% CI -0.58 to 0.15; p = 0.25). Our review supports the association between mood disorders and gluten intake in susceptible individuals. The effects of a GFD on mood in subjects without gluten-related disorders should be considered in future research.