Recent PubMed Articles on Coeliac Disease (External)

Transcription factors operate across disease loci, with EBNA2 implicated in autoimmunity.

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Transcription factors operate across disease loci, with EBNA2 implicated in autoimmunity.

Nat Genet. 2018 05;50(5):699-707

Authors: Harley JB, Chen X, Pujato M, Miller D, Maddox A, Forney C, Magnusen AF, Lynch A, Chetal K, Yukawa M, Barski A, Salomonis N, Kaufman KM, Kottyan LC, Weirauch MT

Abstract
Explaining the genetics of many diseases is challenging because most associations localize to incompletely characterized regulatory regions. Using new computational methods, we show that transcription factors (TFs) occupy multiple loci associated with individual complex genetic disorders. Application to 213 phenotypes and 1,544 TF binding datasets identified 2,264 relationships between hundreds of TFs and 94 phenotypes, including androgen receptor in prostate cancer and GATA3 in breast cancer. Strikingly, nearly half of systemic lupus erythematosus risk loci are occupied by the Epstein-Barr virus EBNA2 protein and many coclustering human TFs, showing gene-environment interaction. Similar EBNA2-anchored associations exist in multiple sclerosis, rheumatoid arthritis, inflammatory bowel disease, type 1 diabetes, juvenile idiopathic arthritis and celiac disease. Instances of allele-dependent DNA binding and downstream effects on gene expression at plausibly causal variants support genetic mechanisms dependent on EBNA2. Our results nominate mechanisms that operate across risk loci within disease phenotypes, suggesting new models for disease origins.

PMID: 29662164 [PubMed - indexed for MEDLINE]

Celiac Disease Prevalence is Increased in Primary Sjögren's Syndrome and Diffuse Systemic Sclerosis: Lessons from a Large Multi-Center Study.

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Celiac Disease Prevalence is Increased in Primary Sjögren's Syndrome and Diffuse Systemic Sclerosis: Lessons from a Large Multi-Center Study.

J Clin Med. 2019 Apr 19;8(4):

Authors: Bartoloni E, Bistoni O, Alunno A, Cavagna L, Nalotto L, Baldini C, Priori R, Fischetti C, Fredi M, Quartuccio L, Carubbi F, Montecucco C, Doria A, Mosca M, Valesini G, Franceschini F, De Vita S, Giacomelli R, Mirabelli G, Bini V, Gabrielli A, Catassi C, Gerli R

Abstract
Association of celiac disease (CD) with systemic autoimmune diseases (ADs) remains controversial. Awareness of CD in these patients is important to prevent complications, including lymphoproliferative disorders. We evaluated previously diagnosed CD prevalence in systemic lupus erythematosus (SLE), primary Sjögren's syndrome (pSS) and systemic sclerosis (SSc) patients in comparison to 14,298 matched controls. All patients were screened for subclinical CD. Data from 1458 unselected consecutive SLE (580), pSS (354) and SSc (524) patients were collected. Previously biopsy-proven CD diagnosis and both CD- and AD-specific features were registered. All patients without previous CD were tested for IgA transglutaminase (TG). Anti-endomysium were tested in positive/borderline IgA TG. Duodenal biopsy was performed in IgA TG/endomysium+ to confirm CD. CD prevalence in AD was compared to that observed in 14,298 unselected sex- and age-matched adults who acted as controls. CD was more prevalent in pSS vs controls (6.78% vs 0.64%, p < 0.0001). A trend towards higher prevalence was observed in SLE (1.38%, p = 0.058) and SSc (1.34%, p = 0.096). Higher CD prevalence was observed in diffuse cutaneous SSc (4.5%, p ≤ 0.002 vs controls). Subclinical CD was found in two SLE patients and one pSS patient. CD diagnosis usually preceded that of AD. Primary SS and SSc-CD patients were younger at AD diagnosis in comparison to non-celiac patients. Autoimmune thyroiditis was associated with pSS and CD. CD prevalence is clearly increased in pSS and diffuse SSc in comparison to the general population. The association of CD with diffuse but not limited SSc may suggest different immunopathogenic mechanisms characterizing the two subsets. CD screening may be considered in pSS and diffuse SSc in young patients, particularly at the time of diagnosis.

PMID: 31010199 [PubMed]

Feralgine™ a New Approach for Iron Deficiency Anemia in Celiac Patients.

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Feralgine™ a New Approach for Iron Deficiency Anemia in Celiac Patients.

Nutrients. 2019 Apr 20;11(4):

Authors: Giancotti L, Talarico V, Mazza GA, Marrazzo S, Gangemi P, Miniero R, Bertini M

Abstract
BACKGROUND: Celiac disease (CD) is an immunologically-mediated disorder characterized by duodenal mucosa villi atrophy. Iron absorption is usually reduced in celiac patients making every kind of oral iron treatment unhelpful because of malasorption. Feralgine™ is a new product that has been demonstrated to be more bioavailable. As such, the aim of our study was to evaluate the absorption of Feralgine™ in adult patients with CD.
METHODS: Twenty-six adults affected by Iron Deficiency Anemia (IDA), of which 14 were also affected by CD and 12 were not affected by CD, were enrolled. An oral iron absorption test (OIAT) was performed in each patient by administrating Feralgine™, and serum iron was evaluated at baseline (T0) and after 2 h (T1) from the oral iron ingestion.
RESULTS: The OIAT was well tolerated in all patients, and, surprisingly, an equivalent statistically significant improvement in serum iron occurred in the two groups of patients (IDA plus CD: T0 = 28.21 µg/dL vs. T1 = 94.14 µg/dL p = 0.004 and IDA without CD: T0 = 34.91 µg/dL vs. T1 = 118.83 µg/dL, p = 0.0003).
CONCLUSIONS: These results demonstrated the high absorption of Feralgine™ in celiac patients, confirming our previous data obtained with Ferrous Bysglicinate in children with CD.

PMID: 31009990 [PubMed - in process]

Individual variations in cardiovascular-disease-related protein levels are driven by genetics and gut microbiome.

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Individual variations in cardiovascular-disease-related protein levels are driven by genetics and gut microbiome.

Nat Genet. 2018 11;50(11):1524-1532

Authors: Zhernakova DV, Le TH, Kurilshikov A, Atanasovska B, Bonder MJ, Sanna S, Claringbould A, Võsa U, Deelen P, Franke L, de Boer RA, Kuipers F, Netea MG, Hofker MH, Wijmenga C, Zhernakova A, Fu J, LifeLines cohort study, BIOS consortium

Abstract
Despite a growing body of evidence, the role of the gut microbiome in cardiovascular diseases is still unclear. Here, we present a systems-genome-wide and metagenome-wide association study on plasma concentrations of 92 cardiovascular-disease-related proteins in the population cohort LifeLines-DEEP. We identified genetic components for 73 proteins and microbial associations for 41 proteins, of which 31 were associated to both. The genetic and microbial factors identified mostly exert additive effects and collectively explain up to 76.6% of inter-individual variation (17.5% on average). Genetics contribute most to concentrations of immune-related proteins, while the gut microbiome contributes most to proteins involved in metabolism and intestinal health. We found several host-microbe interactions that impact proteins involved in epithelial function, lipid metabolism, and central nervous system function. This study provides important evidence for a joint genetic and microbial effect in cardiovascular disease and provides directions for future applications in personalized medicine.

PMID: 30250126 [PubMed - indexed for MEDLINE]

Evidence Supporting Serology-based Pathway for Diagnosing Celiac Disease in Asymptomatic Children From High-risk Groups.

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Evidence Supporting Serology-based Pathway for Diagnosing Celiac Disease in Asymptomatic Children From High-risk Groups.

J Pediatr Gastroenterol Nutr. 2018 04;66(4):641-644

Authors: Paul SP, Sandhu BK, Spray CH, Basude D, Ramani P

Abstract
OBJECTIVE: The European Society for Pediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) guidelines for diagnosing celiac disease (CD) in children were modified in 2012. They recommend that in symptomatic children with anti-tissue transglutaminase antibody (anti-tTG) titer of >10 times upper limit of normal (>10× ULN) and who have positive anti-endomysial antibody and HLA-DQ2/DQ8 haplotype, the diagnosis of CD can be based on serology. The aim of this study is to establish whether serology-based pathway of the ESPGHAN guidelines could also be reliably applied to asymptomatic children from high-risk groups.
METHODS: From March 2007 to February 2017, prospective data on anti-tTG titer, age, sex, and reason for screening were collected at diagnostic endoscopy on all asymptomatic children being diagnosed as having CD. The relationship between modified Marsh-Oberhuber classification histological grading and contemporaneous anti-tTG titers was analyzed.
RESULTS: A total of 157 asymptomatic children were diagnosed as having CD. Eighty-four of 157 (53.5%) had antitTG >10× ULN (normal <10 IU/mL) and 75 of 84 were from high-risk groups. All 75 had definitive histological evidence (Marsh-Oberhuber 3a-3c) of small bowel enteropathy. Fifty-three of 84 children had anti-tTG >200 IU/mL and total villous atrophy was present in 29 of 53 (55%). Main reasons for serological screening were: type-1 diabetes mellitus (n = 36) and first-degree relatives with CD (n = 24). Mean age at diagnosis was 8.8 years. Serology-based diagnosis is cost-beneficial by around £1275 per child in the United Kingdom.
CONCLUSIONS: All 75 asymptomatic children from high-risk groups with anti-tTG >10× ULN had histology-proven CD. This study provides further evidence that the guidelines for diagnosing CD by the serology-based pathway should be extended to these children.

PMID: 28957985 [PubMed - indexed for MEDLINE]

Iron Status in Pediatric Celiac Disease: A Retrospective Chart Review.

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Iron Status in Pediatric Celiac Disease: A Retrospective Chart Review.

J Pediatr Gastroenterol Nutr. 2018 04;66(4):651-653

Authors: Popov J, Baldawi M, Mbuagbaw L, Gould M, Mileski H, Brill H, Pai N

Abstract
The present study assessed the role of serum ferritin as a noninvasive biomarker in the diagnosis and monitoring of pediatric celiac disease. A retrospective chart review was performed on patients younger than 18 years old at time of diagnosis (n = 193) between 1998 and 2015. A total of 653 paired values demonstrated a weak negative correlation between serum ferritin and tissue transglutaminase-immunoglobulin A (r = -0.114; P = 0.004), necessitating further evaluation. A significant relationship was found between reduction of tissue transglutaminase-immunoglobulin A and increase in serum ferritin after institution of a gluten-free diet (P < 0.0001), suggesting that resolution of villous damage is necessary for promoting adequate iron absorption.

PMID: 28953524 [PubMed - indexed for MEDLINE]

The Effect of Gluten-free Diet on Clinical Symptoms and the Intestinal Mucosa of Patients With Potential Celiac Disease.

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The Effect of Gluten-free Diet on Clinical Symptoms and the Intestinal Mucosa of Patients With Potential Celiac Disease.

J Pediatr Gastroenterol Nutr. 2018 04;66(4):654-656

Authors: Mandile R, Discepolo V, Scapaticci S, Del Vecchio MR, Maglio MA, Greco L, Troncone R, Auricchio R

Abstract
In this prospective study, we evaluated the effect of gluten-free diet (GFD) in a cohort of 65 children with potential celiac disease. Patients received GFD for signs/symptoms (N = 47) or parents' choice (N = 18). Most frequent signs/symptoms were low body mass index (36%), recurrent abdominal pain (34%), and diarrhea (19%). Of the 35/47 patients followed-up on GFD, only 54% (19/35) showed a complete clinical response. In 9 of 65 patients an intestinal biopsy was also performed after at least 1 year of GFD. No significant differences were observed in terms of Marsh grade (P = 0.33), lamina propria CD25+ cells (P = 0.80), CD3+ (P = 0.9), and γδ+ (P = 0.59) intraepithelial lymphocytes density and intestinal anti-TG2 deposits (P = 0.60). In conclusion, caution is necessary before attributing all symptoms to gluten in this condition.

PMID: 28922261 [PubMed - indexed for MEDLINE]

Where are we today with Helicobacter pylori infection among healthy children in Saudi Arabia?

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Where are we today with Helicobacter pylori infection among healthy children in Saudi Arabia?

Saudi J Gastroenterol. 2019 Apr 11;:

Authors: Al-Hussaini AA, Al Jurayyan AN, Bashir SM, Alshahrani D

Abstract
Background/Aims: The available studies on Helicobacter pylori (H. pylori) prevalence among healthy asymptomatic population across Saudi Arabia suffers from significant limitations. We conducted this large population-based study to estimate the H. pylori seropositivity rate among apparently healthy children in Saudi Arabia, using anti-H. pylori immunoglobulin A (IgA) and IgG serology tests, and to study the influence of H. pylori infection on growth.
Materials and Methods: We conducted a cross-sectional study to screen apparently healthy school aged Saudi children (aged 6-15 years), attending primary and intermediate schools in Riyadh between 2014 and 2016, for H. pylori seropositivity by checking for the presence of anti-H. pylori IgG and IgA antibodies in serum specimens.
Results: Out of 3551 serum specimens, 1413 cases tested seropositive for H. pylori organism (40%): 430 (12.2%) were both IgG and IgA positive, 212 (6%) and 771 (21.7%) cases showed isolated positivity for IgG or IgA, respectively. Male gender, older age, lower levels of socioeconomic status (SES), and family members >10 were significantly associated with H. pylori seropositivity. The proportion of participants with short stature was significantly more in the H. pylori seropositive group than the seronegative group (OR1.249, confidence interval [1.020-1.531], P= 0.033). There was no significant association between H. pylori seropositivity and gastrointestinal symptoms.
Conclusion: The prevalence of H. pylori seropositivity among apparently healthy Saudi children (40%) is intermediate compared with that in developed and developing countries. The Saudi pediatric population shows a predominant IgA-type immunological response to H. pylori infection.

PMID: 31006713 [PubMed - as supplied by publisher]

Causal relationships among the gut microbiome, short-chain fatty acids and metabolic diseases.

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Causal relationships among the gut microbiome, short-chain fatty acids and metabolic diseases.

Nat Genet. 2019 04;51(4):600-605

Authors: Sanna S, van Zuydam NR, Mahajan A, Kurilshikov A, Vich Vila A, Võsa U, Mujagic Z, Masclee AAM, Jonkers DMAE, Oosting M, Joosten LAB, Netea MG, Franke L, Zhernakova A, Fu J, Wijmenga C, McCarthy MI

Abstract
Microbiome-wide association studies on large population cohorts have highlighted associations between the gut microbiome and complex traits, including type 2 diabetes (T2D) and obesity1. However, the causal relationships remain largely unresolved. We leveraged information from 952 normoglycemic individuals for whom genome-wide genotyping, gut metagenomic sequence and fecal short-chain fatty acid (SCFA) levels were available2, then combined this information with genome-wide-association summary statistics for 17 metabolic and anthropometric traits. Using bidirectional Mendelian randomization (MR) analyses to assess causality3, we found that the host-genetic-driven increase in gut production of the SCFA butyrate was associated with improved insulin response after an oral glucose-tolerance test (P = 9.8 × 10-5), whereas abnormalities in the production or absorption of another SCFA, propionate, were causally related to an increased risk of T2D (P = 0.004). These data provide evidence of a causal effect of the gut microbiome on metabolic traits and support the use of MR as a means to elucidate causal relationships from microbiome-wide association findings.

PMID: 30778224 [PubMed - indexed for MEDLINE]

MicroRNAs link chronic inflammation in childhood to growth impairment and insulin-resistance.

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MicroRNAs link chronic inflammation in childhood to growth impairment and insulin-resistance.

Cytokine Growth Factor Rev. 2018 02;39:1-18

Authors: Cirillo F, Lazzeroni P, Catellani C, Sartori C, Amarri S, Street ME

Abstract
MicroRNAs are involved in multiple pathophysiological networks and in the pathogenesis of a broad spectrum of human disorders, including cancer and inflammatory diseases. Impaired linear growth is encountered in children with chronic inflammatory conditions such as cystic fibrosis, inflammatory bowel diseases, juvenile idiopathic arthritis, celiac disease and in subjects born intrauterine growth restricted/small for gestational age. Children with inflammatory conditions may also be at risk of developing insulin resistance as a result of the inflammatory process and concurrent therapy. Chronic inflammation may lead to a continuum of abnormalities in the Growth hormone/Insulin-like growth factor 1 (GH/IGF-I) axis, including relative GH insufficiency, GH/IGF-I resistance due to down regulation of GH and IGF-I receptors, changes in GH and IGF-I bioavailability due to modifications of binding proteins, and/or impaired GH/IGF-I signaling. The aim of this review is first to summarize the current knowledge concerning microRNAs involved in inflammation in the most relevant chronic inflammatory diseases in childhood, second to provide new insights into miRNA regulation of growth and insulin sensitivity mediated by the inflammatory processes. We evaluated single microRNAs involved in inflammation in the single conditions mentioned above and verified which had validated and predicted targets within the GH receptor, IGF-I type 1 receptor and insulin receptor interactomes. The findings show a new link among inflammation, growth and insulin sensitivity mediated by miRNAs that warrants further research in the future.

PMID: 29398400 [PubMed - indexed for MEDLINE]

Anaphylaxis after wheat ingestion in a patient with coeliac disease: two kinds of reactions and the same culprit food.

Anaphylaxis after wheat ingestion in a patient with coeliac disease: two kinds of reactions and the same culprit food.

Eur J Gastroenterol Hepatol. 2019 Apr 15;:

Authors: Mennini M, Fiocchi A, Trovato CM, Ferrari F, Iorfida D, Cucchiara S, Montuori M

Abstract
In recent years, the role of atopic dermatitis epidermal skin barrier defects in inducing a transcutaneous allergic sensitization is highly debated, possibly explaining why some children with eczema are sensitized to foods they have never eaten. In our specific situation, the association between coeliac disease and wheat allergy might be particularly harmful owing to unavoidable strict food avoidance. We describe the case of a young boy affected by coeliac disease who, after an occasional unexpected ingestion of gluten, experienced a complete anaphylactic reaction characterized by urticarial, labial angioedema, wheezing, and hypotension. To better investigate the state of allergic sensitization to wheat in our patient, we then performed the component resolved diagnosis, which showed Tri a19 2 kU/l and Tri a14 0.3 kU/l. These results demonstrated the association of IgE-mediated allergy to wheat and coeliac disease. The natural course of specific IgE in allergic patients who are on a food-free diet needs further investigation, such as the possible influence that the increasing popularity of gluten-free diets may have on the epidemiology of wheat allergy in westernized societies. National and International registers of cases of anaphylaxis may improve the still limited knowledge in this field. The final message of our contribution is that the decision to eliminate a food should to take into account a patient's awareness of possible consequences.

PMID: 30994495 [PubMed - as supplied by publisher]

Adherence to a Gluten-free Diet: Assessment by Dietician Interview and Serology.

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Adherence to a Gluten-free Diet: Assessment by Dietician Interview and Serology.

J Pediatr Gastroenterol Nutr. 2018 03;66(3):e67-e70

Authors: Mehta P, Pan Z, Riley MD, Liu E

Abstract
We aimed to determine whether tissue transglutaminase (tTG) autoantibody positivity was associated with dietitian-assessed adherence to a gluten-free diet in pediatric patients with celiac disease and identify areas where adherence falters. We reviewed the records of children with celiac disease who had a standardized evaluation of adherence by a registered dietitian. A negative tTG value was not associated with good adherence (P = NS). Adherent and nonadherent children differed with respect to purposeful and accidental gluten exposure (P < 0.0001), knowledge (P = 0.003), cross-contact (P = 0.003), potential exposure via medications and cosmetics (P = 0.004), and potential exposure while at restaurants (P < 0.0001), but not with respect to potential exposure at school (P = NS). Based on our findings, we suggest that negative tTG levels are not necessarily indicative of good adherence to a gluten-free diet in pediatric patients with celiac disease. A separate assessment of adherence is needed focusing on knowledge, behavior while dining out, and intent to adhere.

PMID: 28806297 [PubMed - indexed for MEDLINE]

Rotavirus Vaccination Does Not Increase Type 1 Diabetes and May Decrease Celiac Disease in Children and Adolescents.

Rotavirus Vaccination Does Not Increase Type 1 Diabetes and May Decrease Celiac Disease in Children and Adolescents.

Pediatr Infect Dis J. 2019 May;38(5):539-541

Authors: Hemming-Harlo M, Lähdeaho ML, Mäki M, Vesikari T

Abstract
BACKGROUND: Rotavirus (RV) infection has been proposed to trigger type 1 diabetes mellitus (DM1) and celiac disease (CD) by molecular mimicry in genetically susceptible children. If so, a live attenuated oral RV vaccine could also trigger these autoimmune diseases, or else, prevent the effect of wild-type RV infection.
METHODS: In Rotavirus Efficacy and Safety Trial, conducted between 2001 and 2003, the participant children received RotaTeq (Kenilworth, NJ) vaccine or placebo in 1:1 ratio. The surveillance was extended as Finnish Extension Study. A questionnaire was sent in 2015 to the parents of 19,133 Finnish Extension Study participants and 5764 (30%) returned the questionnaire. Diagnosis of DM1, biopsy-proven CD and other autoimmune disease over the 11-14 year period were inquired.
RESULTS: At the time of questionnaire, the prevalence of DM1 was similar in both groups, 0.97% (25 of 2580 children) in the placebo group and 1.04% (33 of 3184 children) in the vaccine group (P = 0.810). The prevalence of CD was significantly higher in placebo recipients (1.11%; confidence interval: 0.78%-1.6%) than in vaccine recipients (0.60%; confidence interval: 0.38%-0.93%) (P = 0.027).
CONCLUSIONS: RV vaccination using RotaTeq did not alter the occurrence of DM1 but decreased the prevalence of CD in childhood and adolescence. We propose that wild-type RV may trigger CD and the triggering effect can be prevented or reduced by RV vaccination.

PMID: 30986791 [PubMed - in process]

Role of HLA-DQ typing and anti-tTGA antibody titres in diagnosing celiac disease without duodenal biopsy in type 1 diabetes: A study of the population-based pediatric type 1 diabetes cohort of Western Australia.

Role of HLA-DQ typing and anti-tTGA antibody titres in diagnosing celiac disease without duodenal biopsy in type 1 diabetes: A study of the population-based pediatric type 1 diabetes cohort of Western Australia.

Pediatr Diabetes. 2019 Apr 15;:

Authors: Joshi KK, Haynes A, Davis EA, D'Orsogna L, McLean-Tooke A

Abstract
AIM: The primary aim of the current study was to determine if it is cost effective to use HLA typing as a first line screening test for celiac disease (CD) in children with type 1 diabetes (T1D), as recommended by the European Society of Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN). The second aim was to investigate whether anti-tissue transglutaminase IgA (anti-tTGA) antibodies can be used to diagnose CD without the need for a confirmatory duodenal biopsy in T1D.
METHODS: Data for all T1D patients aged < 18 years, who attended the diabetes clinics in Western Australia up to June 2017, were extracted from the Western Australian Children's Diabetes Database (WACDD) and analyzed for their demographic data and CD permissive HLA alleles (DQ2, DQ8 and DQ7). For T1D patients already diagnosed with CD, the mode of diagnosis of CD, anti-tTGA titers and CD permissive HLA alleles were analyzed.
RESULTS: Of the 936 eligible T1D patients identified, HLA-DQ typing was available for 551 (59%). Of these 551 patients, 504 (91.2 %) were positive for celiac permissive HLA alleles. Eight percent (n=75) of the T1D patients had a co-diagnosis of CD. High anti-tTGA titers were observed in those who were diagnosed with a positive duodenal biopsy.
CONCLUSION: HLA-DQ typing is not cost effective as a first line screening test for CD in T1D patients due to over-representation of CD permissive HLA alleles in this group. Anti-tTGA titers may be useful in diagnosing CD in T1D without duodenal biopsy, as high levels were found to be strongly predictive of CD. This article is protected by copyright. All rights reserved.

PMID: 30985044 [PubMed - as supplied by publisher]

Infant milk-feeding practices and diagnosed celiac disease and inflammatory bowel disease in offspring: a systematic review.

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Infant milk-feeding practices and diagnosed celiac disease and inflammatory bowel disease in offspring: a systematic review.

Am J Clin Nutr. 2019 Mar 01;109(Supplement_7):838S-851S

Authors: Güngör D, Nadaud P, Dreibelbis C, LaPergola CC, Wong YP, Terry N, Abrams SA, Beker L, Jacobovits T, Järvinen KM, Nommsen-Rivers LA, O'Brien KO, Oken E, Pérez-Escamilla R, Ziegler EE, Spahn JM

Abstract
BACKGROUND: During the Pregnancy and Birth to 24 Months Project, the USDA and US Department of Health and Human Services initiated an evidence review on diet and health in these populations.
OBJECTIVE: The aim of these systematic reviews was to examine the relationships of never versus ever feeding human milk, shorter versus longer durations of any and exclusive human milk feeding, and feeding a lower versus a higher intensity of human milk to mixed-fed infants with diagnosed celiac disease and inflammatory bowel disease (IBD).
METHODS: The Nutrition Evidence Systematic Review team (formerly called the Nutrition Evidence Library) conducted systematic reviews with external experts. We searched CINAHL, Cochrane, Embase, and PubMed for articles published January, 1980 to March, 2016, dual-screened the results using predetermined criteria, extracted data from and assessed risk of bias for each included study, qualitatively synthesized the evidence, developed conclusion statements, and graded the strength of the evidence.
RESULTS: We included 9 celiac disease and 17 IBD articles. Limited case-control evidence suggests never versus ever being fed human milk is associated with higher risk of celiac disease, but concerns about reverse causality precluded a conclusion about the relationship of shorter versus longer durations of any human milk feeding with celiac disease. Evidence examining never versus ever feeding human milk and IBD was inconclusive, and limited, but consistent, case-control evidence suggests that, among infants fed human milk, shorter versus longer durations of any human milk feeding are associated with higher risk of IBD. For both outcomes, evidence examining the duration of exclusive human milk feeding was scant and no articles examined the intensity of human milk fed to mixed-fed infants.
CONCLUSION: Limited case-control evidence suggests that feeding human milk for short durations or not at all associates with higher risk of diagnosed IBD and celiac disease, respectively. The small number of studies and concern about reverse causality and recall bias prevent stronger conclusions.

PMID: 30982875 [PubMed - in process]

Genistein antagonizes gliadin-induced CFTR malfunction in models of celiac disease.

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Genistein antagonizes gliadin-induced CFTR malfunction in models of celiac disease.

Aging (Albany NY). 2019 Apr 12;:

Authors: Esposito S, Villella VR, Ferrari E, Monzani R, Tosco A, Rossin F, D'Eletto M, Castaldo A, Luciani A, Silano M, Bona G, Marseglia GL, Romani L, Piacentini M, Raia V, Kroemer G, Maiuri L

Abstract
In celiac disease (CD), an intolerance to dietary gluten/gliadin, antigenic gliadin peptides trigger an HLA-DQ2/DQ8-restricted adaptive Th1 immune response. Epithelial stress, induced by other non-antigenic gliadin peptides, is required for gliadin to become fully immunogenic. We found that cystic-fibrosis-transmembrane-conductance-regulator (CFTR) acts as membrane receptor for gliadin-derived peptide P31-43, as it binds to CFTR and impairs its channel function. P31-43-induced CFTR malfunction generates epithelial stress and intestinal inflammation. Maintaining CFTR in an active open conformation by the CFTR potentiators VX-770 (Ivacaftor) or Vrx-532, prevents P31-43 binding to CFTR and controls gliadin-induced manifestations. Here, we evaluated the possibility that the over-the-counter nutraceutical genistein, known to potentiate CFTR function, would allow to control gliadin-induced alterations. We demonstrated that pre-treatment with genistein prevented P31-43-induced CFTR malfunction and an epithelial stress response in Caco-2 cells. These effects were abrogated when the CFTR gene was knocked out by CRISP/Cas9 technology, indicating that genistein protects intestinal epithelial cells by potentiating CFTR function. Notably, genistein protected gliadin-sensitive mice from intestinal CFTR malfunction and gliadin-induced inflammation as it prevented gliadin-induced IFN-γ production by celiac peripheral-blood-mononuclear-cells (PBMC) cultured ex-vivo in the presence of P31-43-challenged Caco-2 cells. Our results indicate that natural compounds capable to increase CFTR channel gating might be used for the treatment of CD.

PMID: 30981209 [PubMed - as supplied by publisher]

Author Correction: Gut microbiome structure and metabolic activity in inflammatory bowel disease.

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Author Correction: Gut microbiome structure and metabolic activity in inflammatory bowel disease.

Nat Microbiol. 2019 Apr 10;:

Authors: Franzosa EA, Sirota-Madi A, Avila-Pacheco J, Fornelos N, Haiser HJ, Reinker S, Vatanen T, Hall AB, Mallick H, McIver LJ, Sauk JS, Wilson RG, Stevens BW, Scott JM, Pierce K, Deik AA, Bullock K, Imhann F, Porter JA, Zhernakova A, Fu J, Weersma RK, Wijmenga C, Clish CB, Vlamakis H, Huttenhower C, Xavier RJ

Abstract
In the Supplementary Tables 2, 4 and 6 originally published with this Article, the authors mistakenly included sample identifiers in the form of UMCGs rather than UMCG IBDs in the validation cohort; this has now been amended.

PMID: 30971771 [PubMed - as supplied by publisher]

Diagnostic delay of pediatric inflammatory bowel disease in Saudi Arabia.

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Diagnostic delay of pediatric inflammatory bowel disease in Saudi Arabia.

Saudi J Gastroenterol. 2019 Apr 05;:

Authors: El Mouzan MI, AlSaleem BI, Hasosah MY, Al Hussaini AA, Al Anazi AH, Saadah OI, Al Sarkhy AA, Al Mofarreh MA, Assiri AA

Abstract
Background/Aim: Delay in the diagnosis of inflammatory bowel disease (IBD) is associated with complications. Our aim was to describe the pattern and risk factors associated with delay in the diagnosis of IBD in Saudi children.
Patients and Methods: This was a multicenter study with a retrospective/prospective design. Data on diagnostic delay in children with Crohn's disease (CD) and ulcerative colitis (UC) were retrieved from physician's notes. Multivariate regression analysis was used to assess the risk factors associated with long delay in diagnosis.
Results: There were 240 and 183 Saudi children with CD and UC, respectively. The median delays in diagnosis were 8 and 5 months in CD and UC, respectively, significantly longer in children with CD than UC (P < 0.001). Long diagnostic delays (>75th percentile) were 24 and 8.8 months for CD and UC, respectively. Ileal location was a significant risk factor in CD and the age of onset above 10 years was protective in UC.
Conclusions: Long diagnostic delay in IBD was mainly due to the longer delay in gastroenterologist consultation. Review of the referral system is needed to focus on measures to reduce long delays in diagnosis. The ileal location as a risk factor in CD and age older than 10 years as protective in UC should help recognition and early referral.

PMID: 30971589 [PubMed - as supplied by publisher]

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