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Comparison of DNA methylation profiles from saliva in Coeliac disease and non-coeliac disease individuals.
Hearn, NL, Chiu, CL, Lind, JM
BMC medical genomics. 2020;(1):16
Abstract
BACKGROUND Coeliac disease (CD) is a autoimmune disease characterised by mucosal inflammation in the small intestine in response to dietary gluten. Genetic factors play a key role with CD individuals carrying either the HLA-DQ2 or HLA-DQ8 haplotype, however these haplotypes are present in half the general population making them necessary but insufficient to cause CD. Epigenetic modifications, including DNA methylation that can change in response to environmental exposure could help to explain how interactions between genes and environmental factors combine to trigger disease development. Identifying changes in DNA methylation profiles in individuals with CD could help discover novel genomic regions involved in the onset and development of CD. METHODS The Illumina InfiniumMethylation450 Beadchip array (HM450) was used to compare DNA methylation profiles in saliva, in CD and non-CD affected individuals. CD individuals who had been diagnosed at least 2 years previously; were on a GFD; and who were currently asymptomatic; were compared to age and sex-matched non-CD affected healthy controls. Bisulphite pyrosequencing was used to validate regions found to be differentially methylated. These regions were also validated in a second larger cohort of CD and non-CD affected individuals. RESULTS Methylation differences within the HLA region at HLA-DQB1 were identified on HM450 but could not be confirmed with pyrosequencing. Significant methylation differences near the SLC17A3 gene were confirmed on pyrosequencing in the initial pilot cohort. Interestingly pyrosequencing sequencing of these same sites within a second cohort of CD and non-CD affected controls produced significant methylation differences in the opposite direction. CONCLUSION Altered DNA methylation profiles appear to be present in saliva in CD individuals. Further work to confirm whether these differences are truly associated with CD is needed.
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Clinical and Microbiological Effect of a Multispecies Probiotic Supplementation in Celiac Patients With Persistent IBS-type Symptoms: A Randomized, Double-Blind, Placebo-controlled, Multicenter Trial.
Francavilla, R, Piccolo, M, Francavilla, A, Polimeno, L, Semeraro, F, Cristofori, F, Castellaneta, S, Barone, M, Indrio, F, Gobbetti, M, et al
Journal of clinical gastroenterology. 2019;(3):e117-e125
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Abstract
GOALS The goals of this study were to evaluate the efficacy and safety of a probiotic mixture in patients with celiac disease (CD) with irritable bowel syndrome (IBS)-type symptoms despite a strict gluten-free diet (GFD). BACKGROUND About 30% of patients with CD adherent to a GFD suffer from IBS-type symptoms; a possible cause resides in the imbalances of the intestinal microbiota in CD. Probiotics may represent a potential treatment. STUDY CD patients with IBS-type symptoms entered a prospective, double-blind, randomized placebo-controlled study. A 6-week treatment period was preceded by a 2-week run-in and followed by a 6-week follow-up phase. Clinical data were monitored throughout the study by validated questionnaires: IBS Severity Scoring System (IBS-SSS); Gastrointestinal Symptom Rating Scale (GSRS); Bristol Stool Form Scale (BSFS); and IBS Quality of Life Questionnaire (IBS-QOL). The fecal microbiota were assayed using plate counts and 16S rRNA gene-based analysis. RESULTS In total, 109 patients were randomized to probiotics (n=54) or placebo (n=55). IBS-SSS and GSRS decreased significantly in probiotics, as compared with placebo [(-15.9%±14.8% vs. 8.2%±25.9%; P<0.001) and (-19.8%±16.6% vs. 12.9%±31.6%; P<0.001)], respectively. Treatment success was significantly higher in patients receiving probiotics, as compared with placebo (15.3% vs. 3.8%; P<0.04). Presumptive lactic acid bacteria, Staphylococcus and Bifidobacterium, increased in patients receiving probiotic treatment. No adverse events were reported. CONCLUSIONS A 6-week probiotic treatment is effective in improving the severity of IBS-type symptoms, in CD patients on strict GFD, and is associated with a modification of gut microbiota, characterized by an increase of bifidobacteria.
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Adherence to the Gluten-free Diet and Health-related Quality of Life in an Ethnically Diverse Pediatric Population With Celiac Disease.
Mager, DR, Marcon, M, Brill, H, Liu, A, Radmanovich, K, Mileski, H, Nasser, R, Alzaben, A, Carroll, MW, Yap, J, et al
Journal of pediatric gastroenterology and nutrition. 2018;(6):941-948
Abstract
OBJECTIVES Celiac disease (CD) is an autoimmune disease that requires lifelong adherence to a gluten-free diet (GFD). Adherence to the GFD in childhood may be poor and adversely influence health-related quality of life (HRQOL). The study purpose was to determine sociodemographic and socioeconomic factors influencing adherence to the GFD and HRQOL in a multiethnic cohort of youth with CD. METHODS A multisite (Edmonton, Hamilton, Toronto) study examining child-parent HRQOL in youth with CD (n = 243) and/or mild gastrointestinal complaints (GI-CON; n = 148) was conducted. Sociodemographic (age, child-parental age/education/ethnicity/place of birth), anthropometric (weight, height, body mass index), disease (diagnosis, age at diagnosis, duration, Marsh score, serology), household characteristics (income, family size, region, number of children/total household size), HRQOL (Peds TM/KINDL and Celiac Disease DUX), GI Complaints (PedsQL: Gastrointestinal Symptom Scale) and gluten intake were measured. RESULTS Younger age (<10 years), non-Caucasian ethnicity (parent/child), and presence of GI symptoms were associated with the highest rates of adherence to the GFD in CD children (P < 0.05). CD children (parent/child) had higher HRQOL (average, composite domains) than GI-CON (P < 0.05), but CD children were comparable to healthy children. Lack of GI symptoms, non-Caucasian ethnicity and age (<10 years) were associated with increased HRQOL in composite/average domains for CD (P < 0.05). CONCLUSIONS Child-parent perceptions of HRQOL in a multiethnic population with CD are comparable to healthy reference populations, but significantly higher than in parent/child GI-CON. Adherence to the GFD in ethnically diverse youth with CD was related to GI symptoms, age of the child, and ethnicity of the parent-child.
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Role of capsule endoscopy in suspected celiac disease: A European multi-centre study.
Luján-Sanchis, M, Pérez-Cuadrado-Robles, E, García-Lledó, J, Juanmartiñena Fernández, JF, Elli, L, Jiménez-García, VA, Egea-Valenzuela, J, Valle-Muñoz, J, Carretero-Ribón, C, Fernández-Urién-Sainz, I, et al
World journal of gastroenterology. 2017;(4):703-711
Abstract
AIM: To analyze the diagnostic yield (DY), therapeutic impact (TI) and safety of capsule endoscopy (CE). METHODS This is a multi-centre, observational, analytical, retrospective study. A total of 163 patients with suspicion of celiac disease (CD) (mean age = 46.4 ± 17.3 years, 68.1% women) who underwent CE from 2003 to 2015 were included. Patients were divided into four groups: seronegative CD with atrophy (Group-I, n = 19), seropositive CD without atrophy (Group-II, n = 39), contraindication to gastroscopy (Group-III, n = 6), seronegative CD without atrophy, but with a compatible context (Group-IV, n = 99). DY, TI and the safety of CE were analysed. RESULTS The overall DY was 54% and the final diagnosis was villous atrophy (n = 65, 39.9%), complicated CD (n = 12, 7.4%) and other enteropathies (n = 11, 6.8%; 8 Crohn's). DY for groups I to IV was 73.7%, 69.2%, 50% and 44.4%, respectively. Atrophy was located in duodenum in 24 cases (36.9%), diffuse in 19 (29.2%), jejunal in 11 (16.9%), and patchy in 10 cases (15.4%). Factors associated with a greater DY were positive serology (68.3% vs 49.2%, P = 0.034) and older age (P = 0.008). On the other hand, neither sex nor clinical presentation, family background, positive histology or HLA status were associated with DY. CE results changed the therapeutic approach in 71.8% of the cases. Atrophy was associated with a greater TI (92.3% vs 45.3%, P < 0.001) and 81.9% of the patients responded to diet. There was one case of capsule retention (0.6%). Agreement between CE findings and subsequent histology was 100% for diagnosing normal/other conditions, 70% for suspected CD and 50% for complicated CD. CONCLUSION CE has a high DY in cases of suspicion of CD and it leads to changes in the clinical course of the disease. CE is safe procedure with a high degree of concordance with histology and it helps in the differential diagnosis of CD.
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Advanced glycation end products (AGEs) and the soluble receptor for AGE (sRAGE) in patients with type 1 diabetes and coeliac disease.
Bakker, SF, Tushuizen, ME, Gözütok, E, Çiftci, A, Gelderman, KA, Mulder, CJ, Simsek, S
Nutrition, metabolism, and cardiovascular diseases : NMCD. 2015;(2):230-5
Abstract
BACKGROUND AND AIMS Advanced glycation end (AGE) products play a role in the progression of diabetic complications. Gluten-free diet (GFD) might affect AGE levels in patients who adhere to a GFD because of coeliac disease (CD). The aim of our study was to compare skin AGE levels and soluble receptor AGE levels (sRAGE) in patients with type 1 diabetes (T1DM) with (T1DM + CD) and without CD (T1DM - CD) and healthy controls. METHODS AND RESULTS We recruited 25 T1DM + CD and 25 T1DM - CD patients, matched for age, gender, diabetes duration, and glycaemic control alongside 25 healthy controls. We collected demographic, clinical and biochemical characteristics, including skin autofluorescence (AF), sRAGE and hs-CRP levels. The duration of T1DM in patients was 30 ± 14 (+CD) and 29 ± 14 years (-CD), whereas CD duration in T1DM + CD patients was 14 ± 10 years. Skin AF levels in T1DM patients were higher compared to healthy controls (2.5 ± 0.6 versus 1.9 ± 0.4, p < 0.01) and skin AF was independently associated with age (r = 0.72, p < 0.01). sRAGE levels were higher in T1DM - CD patients compared to healthy controls (1554 ± 449 versus 1309 ± 400, p = 0.049) and independently associated with creatinine levels (r = 0.32, p < 0.01). CONCLUSION Our study demonstrates that skin AGE and sRAGE levels are elevated in T1DM patients compared with healthy controls. No difference in skin AF or sRAGE levels between T1DM patients with or without CD were observed. The present study suggests that differences in microvascular complications between T1DM and T1DM + CD patients are not due to differences in skin AF or sRAGE levels.
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Might gluten traces in wheat substitutes pose a risk in patients with celiac disease? A population-based probabilistic approach to risk estimation.
Gibert, A, Kruizinga, AG, Neuhold, S, Houben, GF, Canela, MA, Fasano, A, Catassi, C
The American journal of clinical nutrition. 2013;(1):109-16
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Abstract
BACKGROUND In patients with treated celiac disease (CD), the ingestion of gluten traces contained in gluten-free (GF) wheat substitutes (eg, GF bread, flour, and pasta) could cause persisting intestinal mucosal damage. OBJECTIVE The objective was to evaluate the proportion of CD patients at risk of mucosal damage due to the consumption of GF products in 4 European countries (Italy, Spain, Germany, and Norway). DESIGN A probabilistic modeling approach was used to assess the risk of gluten intake at the population level. The input variables were 1) consumption of GF products, 2) concentration of gluten traces in GF products determined by the sandwich R5 ELISA method, and 3) the gluten threshold for mucosal damage of 10 to 50 mg/d. Different population and product availability scenarios were examined for risk assessment. RESULTS The gluten content of 205 commercially available GF products ranged between <5 and 27.8 mg/kg. Overall, 99.5% of the analyzed samples had a gluten concentration <20 mg/kg. Most (94%) had a gluten concentration below the limit of quantification (5 mg/kg). The mean percentage of the CD European population at risk of mucosal damage resulting from consumption of GF products ranged between 0.01 (Germany) and 0.15 (Italy) and remained very low, even in the worst-case scenario (<1%). CONCLUSIONS The adoption of a single gluten threshold (20 mg/kg) for gluten contamination is suggested. GF products in Europe constitute a very safe option for patients with CD. The dietary follow-up of CD patients should focus on other potential sources of gluten contamination.
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Comparative analysis of conventional training and a computer-based interactive training program for celiac disease patients.
Meyer, KG, Fasshauer, M, Nebel, IT, Paschke, R
Patient education and counseling. 2004;(3):353-60
Abstract
Gluten-free diet (GFD) protects against the complications of celiac disease (CD). However, training in the dietetic field is rare in Germany. Thus, CD patients are likely to benefit from a computer-based interactive training program (CBITP) combined with interactive exercises. We compared a CBITP and a conventional training for CD patients regarding increased knowledge, transferability and sustainability. In that context we analyzed whether CD patients are more able to judge the risk of a food or a situation after practicing with the interactive training software. Sixty-four CD patients were included and randomized in two groups. While the first group used the CBITP, the control group received written instructions. Before and after taking part in the training program and 3 weeks later, the participants filled in a questionnaire for celiac knowledge. The results show that both intervention and control groups increased knowledge about CD. However, the intervention group showed significantly better outcome. A CBITP significantly increases knowledge and sustainability as compared to a conventional training for CD patients. CBITPs can enhance patients' training and treatment.