Recent PubMed Articles on Coeliac Disease (External)

Genetic susceptibility for celiac disease is highly prevalent in the Saudi population.

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Genetic susceptibility for celiac disease is highly prevalent in the Saudi population.

Saudi J Gastroenterol. 2018 Sep-Oct;24(5):268-273

Authors: Al-Hussaini A, Alharthi H, Osman A, Eltayeb-Elsheikh N, Chentoufi A

Abstract
Background/Aim: To determine the frequency of celiac disease (CD)-predisposing human leukocyte antigen (HLA)-DQ genotypes in the Saudi population, where the prevalence of CD is 1.5% as recently reported in a mass screening study.
Patients and Methods: In a cross-sectional population-based study, a total of 192 randomly selected healthy school children (97 females, mean age 10.5 ± 2.2 years, all negative for tissue transglutaminase-IgA) were typed for D QA1 and D QB1 genes by polymerase chain reaction sequence-specific oligonucleotide probes.
Results: Of the 192 children, 52.7% carried the high-risk CD-associated HLA-DQ molecules: homozygous DQ2.5 ( 2.6%), DQ2.5/DQ2.2 ( 4.7%), heterozygous DQ2.5 ( 28.15%), homozygous DQ8 ( 4.2%), DQ8/DQ2.2 ( 3.6%), and double dose DQ2.2 ( 9.4%). Low-risk CD-associated HLA-DQ molecules (single dose DQ2.2 and heterozygous DQ8) constituted 3.6% and 9.4%, respectively. Among the very low-risk groups, individuals lacking alleles that contribute to DQ2/DQ8 variants (33.5%), 13.5% carried only one of the alleles of the high-risk HLA-DQ2.5 heterodimer called "half-heterodimer" (HLA-DQA1*05 in 12% and HLA-DQB1* 02 in 1.5%), and 20.8% lacked all the susceptible alleles (DQX.x). Gender distribution was not significantly different among the CD-risk groups.
Conclusion: We report one of the highest frequencies of CD-predisposing HLA-DQ genotypes among healthy general populations (52.7%) worldwide, which might partly explain the high prevalence of CD in the Saudi community.

PMID: 29956690 [PubMed - indexed for MEDLINE]

IL-10 signaling prevents gluten-dependent intraepithelial CD4+ cytotoxic T lymphocyte infiltration and epithelial damage in the small intestine.

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IL-10 signaling prevents gluten-dependent intraepithelial CD4+ cytotoxic T lymphocyte infiltration and epithelial damage in the small intestine.

Mucosal Immunol. 2018 Dec 12;:

Authors: Costes LMM, Lindenbergh-Kortleve DJ, van Berkel LA, Veenbergen S, Raatgeep HRC, Simons-Oosterhuis Y, van Haaften DH, Karrich JJ, Escher JC, Groeneweg M, Clausen BE, Cupedo T, Samsom JN

Abstract
Breach of tolerance to gluten leads to the chronic small intestinal enteropathy celiac disease. A key event in celiac disease development is gluten-dependent infiltration of activated cytotoxic intraepithelial lymphocytes (IELs), which cytolyze epithelial cells causing crypt hyperplasia and villous atrophy. The mechanisms leading to gluten-dependent small intestinal IEL infiltration and activation remain elusive. We have demonstrated that under homeostatic conditions in mice, gluten drives the differentiation of anti-inflammatory T cells producing large amounts of the immunosuppressive cytokine interleukin-10 (IL-10). Here we addressed whether this dominant IL-10 axis prevents gluten-dependent infiltration of activated cytotoxic IEL and subsequent small intestinal enteropathy. We demonstrate that IL-10 regulation prevents gluten-induced cytotoxic inflammatory IEL infiltration. In particular, IL-10 suppresses gluten-induced accumulation of a specialized population of cytotoxic CD4+CD8αα+ IEL (CD4+ CTL) expressing Tbx21, Ifng, and Il21, and a disparate non-cytolytic CD4+CD8α- IEL population expressing Il17a, Il21, and Il10. Concomitantly, IL-10 suppresses gluten-dependent small intestinal epithelial hyperproliferation and upregulation of stress-induced molecules on epithelial cells. Remarkably, frequencies of granzyme B+CD4+CD8α+ IEL are increased in pediatric celiac disease patient biopsies. These findings demonstrate that IL-10 is pivotal to prevent gluten-induced small intestinal inflammation and epithelial damage, and imply that CD4+ CTL are potential new players into these processes.

PMID: 30542112 [PubMed - as supplied by publisher]

Gut microbiome structure and metabolic activity in inflammatory bowel disease.

Gut microbiome structure and metabolic activity in inflammatory bowel disease.

Nat Microbiol. 2018 Dec 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
The inflammatory bowel diseases (IBDs), which include Crohn's disease (CD) and ulcerative colitis (UC), are multifactorial chronic conditions of the gastrointestinal tract. While IBD has been associated with dramatic changes in the gut microbiota, changes in the gut metabolome-the molecular interface between host and microbiota-are less well understood. To address this gap, we performed untargeted metabolomic and shotgun metagenomic profiling of cross-sectional stool samples from discovery (n = 155) and validation (n = 65) cohorts of CD, UC and non-IBD control patients. Metabolomic and metagenomic profiles were broadly correlated with faecal calprotectin levels (a measure of gut inflammation). Across >8,000 measured metabolite features, we identified chemicals and chemical classes that were differentially abundant in IBD, including enrichments for sphingolipids and bile acids, and depletions for triacylglycerols and tetrapyrroles. While > 50% of differentially abundant metabolite features were uncharacterized, many could be assigned putative roles through metabolomic 'guilt by association' (covariation with known metabolites). Differentially abundant species and functions from the metagenomic profiles reflected adaptation to oxidative stress in the IBD gut, and were individually consistent with previous findings. Integrating these data, however, we identified 122 robust associations between differentially abundant species and well-characterized differentially abundant metabolites, indicating possible mechanistic relationships that are perturbed in IBD. Finally, we found that metabolome- and metagenome-based classifiers of IBD status were highly accurate and, like the vast majority of individual trends, generalized well to the independent validation cohort. Our findings thus provide an improved understanding of perturbations of the microbiome-metabolome interface in IBD, including identification of many potential diagnostic and therapeutic targets.

PMID: 30531976 [PubMed - as supplied by publisher]

Frequency of HLA-DQ, susceptibility genotypes for celiac disease, in Brazilian newborns.

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Frequency of HLA-DQ, susceptibility genotypes for celiac disease, in Brazilian newborns.

Mol Genet Genomic Med. 2018 09;6(5):779-784

Authors: Almeida FC, Gandolfi L, Costa KN, Picanço MRA, Almeida LM, Nóbrega YKM, Pratesi R, Pratesi CB, Selleski N

Abstract
BACKGROUND: The frequency of HLA-DQ2 and DQ8 predisposing genotypes for celiac disease (CD) has shown significant variation among different world regions and has not been previously determined among the highly interbred Brazilian population. The aim of this study was to investigate the frequency of these genotypes among Brazilian newborns (NB).
METHODS: We typed DQA1*05 - DQB1*02 (DQ2.5) and DQA1*03 - DQB1*03:02 (DQ8) alleles in 329 NB using qPCR technique. Subsequently we confirmed our results by PCR-SSP using a reference kit which further identified DQ2.2 (DQA1*02:01 - DQB1*02).
RESULTS: Among the 329 NB, using qPCR technique: 5 (1.52%) carried both DQ2.5 and DQ8 variants; 58 (17.63%) carried only DQ2.5 (DQA1*05 and DQB1*02) and 47 (14.29%) carried only the DQ8 (DQA1*03 and DQB1*03:02) variant. The use of the PCR-SSP method yielded further information; among the 329 samples: 34 (10.34%) tested positive for DQ2.2 and among the 47 previously DQ8 positives samples, we found 10 (3.04%) that also tested positives for DQ2.2.
CONCLUSION: 43.7% of the analyzed individual tested positive for at least one of the CD predisposing HLA-DQ genotypes in our group of Brazilian NB. The highest frequency was found for DQ2.5 positive subjects (17.6%) followed by DQ8 (11.3%); DQ2.2 (10.3%); DQ8 and DQ2.2 (3.0%); DQ2.5 and DQ8 (1.5%). We found no positive sample for DQ2.5 associated with DQ2.2.

PMID: 30014583 [PubMed - indexed for MEDLINE]

The impact of human breast milk components on the infant metabolism.

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The impact of human breast milk components on the infant metabolism.

PLoS One. 2018;13(6):e0197713

Authors: Hellmuth C, Uhl O, Demmelmair H, Grunewald M, Auricchio R, Castillejo G, Korponay-Szabo IR, Polanco I, Roca M, Vriezinga SL, Werkstetter KJ, Koletzko B, Mearin ML, Kirchberg FF

Abstract
BACKGROUND & AIMS: Breastfeeding is beneficial for mothers and infants. Underlying mechanisms and biochemical mediators thus need to be investigated to develop and support improved infant nutrition practices promoting the child health. We analysed the relation between maternal breast milk composition and infant metabolism.
METHODS: 196 pairs of mothers and infants from a European research project (PreventCD) were studied. Maternal milk samples collected at month 1 and month 4 after birth were analysed for macronutrient classes, hormone, and fatty acid (FA) content. Phospholipids, acylcarnitines, and amino acids were measured in serum samples of 4-month old infants. Associations between milk components and infant metabolites were analysed with spearman correlation and linear mixed effect models (LME). P-values were corrected for multiple testing (PLME).
RESULTS: Month 1 milk protein content was strongly associated with infant serum lyso-phosphatidylcholine (LPC) 14:0 (PLME = 0.009). Month 1 milk insulin was associated to infant acetylcarnitine (PLME = 0.01). There were no associations between milk protein content and serum amino acids and milk total fat content and serum polar lipids. Middle- and odd-chain FA% in breast milk at both ages were significantly related to serum LPC and sphingomyelins (SM) species in infant serum (all PLME<0.05), while FA% 20:5n-3 and 22:6n-3 percentages were significantly associated to serum LPC 22:6 (PLME = 1.91×10-4/7.93×10-5) in milk only at month 4. Other polyunsaturated fatty acids and hormones in milk showed only weak associations with infant serum metabolites.
CONCLUSIONS: Infant serum LPC are influenced by breast milk FA composition and, intriguingly, milk protein content in early but not late lactation. LPC 14:0, previously found positively associated with obesity risk, was the serum metabolite which was the most strongly associated to milk protein content. Thus, LPC 14:0 might be a key metabolite not only reflecting milk protein intake in infants, but also relating high protein content in milk or infant formula to childhood obesity risk.

PMID: 29856767 [PubMed - indexed for MEDLINE]

Celiac Disease: A Review of Current Concepts in Pathogenesis, Prevention, and Novel Therapies.

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Celiac Disease: A Review of Current Concepts in Pathogenesis, Prevention, and Novel Therapies.

Front Pediatr. 2018;6:350

Authors: Tye-Din JA, Galipeau HJ, Agardh D

Abstract
Our understanding of celiac disease and how it develops has evolved significantly over the last half century. Although traditionally viewed as a pediatric illness characterized by malabsorption, it is now better seen as an immune illness with systemic manifestations affecting all ages. Population studies reveal this global disease is common and, in many countries, increasing in prevalence. These studies underscore the importance of specific HLA susceptibility genes and gluten consumption in disease development and suggest that other genetic and environmental factors could also play a role. The emerging data on viral and bacterial microbe-host interactions and their alterations in celiac disease provides a plausible mechanism linking environmental risk and disease development. Although the inflammatory lesion of celiac disease is complex, the strong HLA association highlights a central role for pathogenic T cells responding to select gluten peptides that have now been defined for the most common genetic form of celiac disease. What remains less understood is how loss of tolerance to gluten occurs. New insights into celiac disease are now providing opportunities to intervene in its development, course, diagnosis, and treatment.

PMID: 30519552 [PubMed]

Microbiota profile in new-onset pediatric Crohn's disease: data from a non-Western population.

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Microbiota profile in new-onset pediatric Crohn's disease: data from a non-Western population.

Gut Pathog. 2018;10:49

Authors: El Mouzan MI, Winter HS, Assiri AA, Korolev KS, Al Sarkhy AA, Dowd SE, Al Mofarreh MA, Menon R

Abstract
Background: The role of microbiota in Crohn's disease (CD) is increasingly recognized. However, most of the reports are from Western populations. Considering the possible variation from other populations, the aim of this study was to describe the microbiota profile in children with CD in Saudi Arabia, a non-Western developing country population.
Results: Significantly more abundant genera in children with CD included Fusobacterium, Peptostreptococcus, Psychrobacter, and Acinetobacter; whereas the most significantly-depleted genera included Roseburia, Clostridium, Ruminococcus, Ruminoclostridium, Intestinibacter, Mitsuokella, Megasphaera, Streptococcus, Lactobacillus, Turicibacter, and Paludibacter. Alpha diversity was significantly reduced in stool (p = 0.03) but not in mucosa (p = 0.31). Beta diversity showed significant difference in community composition between control and CD samples (p = 0.03).
Conclusion: In this developing country, we found a pattern of microbiota in children with CD similar to Western literature, suggesting a role of recent dietary lifestyle changes in this population on microbiota structure.

PMID: 30519287 [PubMed]

Questionnaire showed that Swedish paediatric clinics complied well with the revised European guidelines for diagnosing coeliac disease.

Questionnaire showed that Swedish paediatric clinics complied well with the revised European guidelines for diagnosing coeliac disease.

Acta Paediatr. 2018 Nov 29;:

Authors: Myléus A, Stenhammar L, Högberg L, Browaldh L, Daniels IM, Fagerberg UL, Gudjónsdóttir AH, Malmquist M, Sandström O, Ivarsson A

Abstract
AIM: In 2012, revised criteria for diagnosing childhood coeliac disease were published by the European Society for Paediatric Gastroenterology, Hepatology and Nutrition and incorporated into the revised Swedish guidelines the same year. These made it possible, in certain cases, to diagnose coeliac disease without taking small bowel biopsies. This survey assessed the extent to which the new guidelines were implemented by Swedish paediatric clinics two years after their introduction.
METHODS: In October 2014, we distributed a paper questionnaire including five questions on diagnostic routines to the 40 paediatric clinics in university or regional hospitals in Sweden that perform small bowel biopsies.
RESULTS: All 36 (90%) clinics that responded used anti-tissue transglutaminase antibodies as the initial diagnostic test and some also used serological markers. Most clinics (81%) used endoscopy and took multiple duodenal biopsies, whereas only a few (19%) occasionally employed a suction capsule. Almost all clinics (86%) omitted taking small bowel biopsies in symptomatic children with repeatedly high coeliac serology and positive genotyping, thereby avoiding the need for invasive endoscopy under anaesthesia.
CONCLUSION: The 2012 Swedish Paediatric Coeliac Disease Diagnostic Guidelines had been widely accepted and implemented in routine healthcare two years after their introduction. This article is protected by copyright. All rights reserved.

PMID: 30496613 [PubMed - as supplied by publisher]

Celiac Disease in Children with Chronic Diarrhoea Attending At Paediatric Gastroenterology and Nutrition Department of BSMMU.

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Celiac Disease in Children with Chronic Diarrhoea Attending At Paediatric Gastroenterology and Nutrition Department of BSMMU.

Mymensingh Med J. 2018 Oct;27(4):820-825

Authors: Parveen S, Karim AB, Rahman SM, Alam MR, Ahmed DS, Rahman MZ

Abstract
This descriptive, cross sectional study was conducted at Bangabandhu Sheikh Mujib Medical University from July 2012 to July 2015 to see the occurrence of celiac disease in children with chronic diarrhea. A total of 62 children (age <18 years) attending the Paediatric Gastroenterology and Nutrition department of BSMMU with chronic diarrhoea were enrolled for the study. Mean age of studied children was 7.87±4.67 years. Ratio of the male and female was 2.27:1. Maximum (66.1%) children came from middle income class family. Out of 62 children with chronic diarrhea, 35.5% (22) were positive for IgA anti-tTG of whom female were 11.3% and male 24.2%. Mean duration of diarrhoea was 44.07±21.77 months in serology positive patients and 34.49±30.52 months in serology negative patients. The age group, 10-14 year showed the highest (50%) prevalence of positive anti-tTG. In the tTG positive group mean Hb was 9.6±1.14gm/dl and which is lower than that in tTG negative group (11.7±1.47gm/dl). Among 22 seropositive patients, histological changes compatible with CD were found in 19 (86.3%) cases and normal in 3 cases. Histological changes were of 3c category of Marsh was found in 3(15.8%) cases, 3b in 4(21.1%) cases and 3a in 12(63.2%) cases. In conclusion, Screening for celiac disease may be included in diagnostic tests for evaluating chronic diarrhoea in children.

PMID: 30487500 [PubMed - in process]

Onset of menarche is not delayed in Slovenian patients with celiac disease.

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Onset of menarche is not delayed in Slovenian patients with celiac disease.

J Int Med Res. 2018 Nov 26;:300060518812623

Authors: Mičetić-Turk D, Vlaisavljević V, Turk E, Pogačar MŠ

Abstract
OBJECTIVE: Celiac disease (CD) is an autoimmune disorder associated with numerous health problems, including reproductive disorders. This study was performed to analyze the association between CD and the menstrual cycle in a group of patients with CD and compare these patients' characteristics with those of healthy women.
METHODS: The study included 145 patients with CD (age, 15-51 years) and 162 healthy women (age, 18-55 years). Age at menarche and characteristics of the menstrual cycle were obtained by an anonymous questionnaire developed for the study.
RESULTS: The age at onset of menarche was 12 to 14 years in 72.9% of the patients with CD and 77.3% of the healthy controls. For most patients (74.2%), the length of the menstrual cycle was around 27 to 28 days with 4 to 5 days of bleeding. Furthermore, 8.4% of patients versus 5.9% of controls experienced bleeding between cycles.
CONCLUSIONS: Our results suggest that in Slovenia, the age at menarche in patients with CD is 12.7 years, which is comparable with that in healthy women. We conclude that CD (treated or untreated) may not be associated with late menarche.

PMID: 30477370 [PubMed - as supplied by publisher]

Probiotics in Celiac Disease.

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Probiotics in Celiac Disease.

Nutrients. 2018 Nov 23;10(12):

Authors: Cristofori F, Indrio F, Miniello VL, De Angelis M, Francavilla R

Abstract
Recently, the interest in the human microbiome and its interplay with the host has exploded and provided new insights on its role in conferring host protection and regulating host physiology, including the correct development of immunity. However, in the presence of microbial imbalance and particular genetic settings, the microbiome may contribute to the dysfunction of host metabolism and physiology, leading to pathogenesis and/or the progression of several diseases. Celiac disease (CD) is a chronic autoimmune enteropathy triggered by dietary gluten exposure in genetically predisposed individuals. Despite ascertaining that gluten is the trigger in CD, evidence has indicated that intestinal microbiota is somehow involved in the pathogenesis, progression, and clinical presentation of CD. Indeed, several studies have reported imbalances in the intestinal microbiota of patients with CD that are mainly characterized by an increased abundance of Bacteroides spp. and a decrease in Bifidobacterium spp. The evidence that some of these microbial imbalances still persist in spite of a strict gluten-free diet and that celiac patients suffering from persistent gastrointestinal symptoms have a desert gut microbiota composition further support its close link with CD. All of this evidence gives rise to the hypothesis that probiotics might play a role in this condition. In this review, we describe the recent scientific evidences linking the gut microbiota in CD, starting from the possible role of microbes in CD pathogenesis, the attempt to define a microbial signature of disease, the effect of a gluten-free diet and host genetic assets regarding microbial composition to end in the exploration of the proof of concept of probiotic use in animal models to the most recent clinical application of selected probiotic strains.

PMID: 30477107 [PubMed - in process]

Screening for autoimmune thyroiditis and celiac disease in minority children with type 1 diabetes.

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Screening for autoimmune thyroiditis and celiac disease in minority children with type 1 diabetes.

J Pediatr Endocrinol Metab. 2018 Aug 28;31(8):879-885

Authors: Kochummen E, Marwa A, Umpaichitra V, Perez-Colon S, Chin VL

Abstract
BACKGROUND: Hashimoto's thyroiditis (HT) and celiac disease (CD) are commonly associated with type 1 diabetes (T1DM). There is no consensus on screening, however, the American Diabetes Association (ADA) and the International Society for Pediatric and Adolescent Diabetes (ISPAD) recommend testing for thyroid function (TFT), thyroid antibodies and anti-tissue transglutaminase antibodies (TTG) IgA soon after diagnosis. TFT should be repeated every 1-2 years while TTG IgA should be tested for within 2 and 5 years. We hypothesize that the rate of HT and CD in our T1DM children is lower, so screening may need to be revised to reflect their underlying risk.
METHODS: An Institutional Review Board (IRB)-approved retrospective chart review was conducted on children with T1DM in the past 10 years. Age, sex, race, A1C, TFT, thyroid and celiac antibodies were obtained. t-Tests, the Wilcoxon-Mann-Whitney test and stepwise regression were performed.
RESULTS: Of 222 children with T1DM, with a mean age of 15.8±5.53 years, followed for 6.1±4.0 years, 53% female, mean A1C 11.1±1.9% and 87% African American (AA). Three had Graves' disease (1.3%), three had HT (1.3%) and 97% were euthyroid. TFT were assessed on average every 1.3 years and thyroid antibodies every 2.5 years. Positive thyroid antibody was found in 11%, negative in 57% and unknown in 32%. The positive antibody group had higher mean A1C and TSH. No biopsy confirmed cases of CD (0%) were found when screened every 2.3 years.
CONCLUSIONS: The number of individuals who screened positive for hypothyroid HT and CD was lower than expected in our population. Further studies are needed to assess the optimal screening frequency for HT and CD in minority children with T1DM.

PMID: 29949512 [PubMed - indexed for MEDLINE]

Ten years of follow-up of the Spanish cohort of the European PreventCD study: the lessons learned.

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Ten years of follow-up of the Spanish cohort of the European PreventCD study: the lessons learned.

Rev Esp Enferm Dig. 2018 08;110(8):493-499

Authors: Crespo Escobar P, Castillejo G, Martínez-Ojinaga E, Donat E, Polanco I, Mearin ML, Ribes-Koninckx C

Abstract
AIM: to evaluate the influence of gluten consumption on celiac disease development and to describe its natural history in the Spanish cohort of the European PreventCD study.
METHODS: prospective multi-center double blind study of 225 children that were followed up from birth. All cases were HLA-DQ2/HLA-DQ8 positive with a 1st degree relative with celiac disease and were followed up in three centers from Madrid, Reus and Valencia. Gluten intake was determined between four and ten months according to the protocol. Gluten intake was ad libitum between eleven and 36 months and was prospectively quantified by means of dietary records. Clinical visits and specific antibody analysis for celiac disease were performed periodically.
RESULTS: twenty-six cases were diagnosed, all had a positive biopsy and serology; 21 had gastrointestinal symptoms and five were asymptomatic. In addition, 2,565 food records were analyzed and statistically significant differences (p < 0.001) were found with regard to gluten consumption among the three centers, although not between celiac and non-celiac children (p = 0.025). The HLA-DQ2.5/DQ2.5 and DQ2.5/DQ2.2 genotypes had a relative risk of 4.7 (95% CI: 0.80-27.55; p = 0.08), which was higher than for the rest of genotypes. Female gender also had a relative risk that was five times higher than that for males.
CONCLUSIONS: the amount of gluten intake between 11 and 36 months or the duration of breast feeding were not risk factors for the development of CD in the Spanish population. The HLA genotype and gender were the most relevant associated factors. In this at-risk group, the disease presented before two years of age in the majority of the cases with a weak clinical expression.

PMID: 29699403 [PubMed - indexed for MEDLINE]

Interplay between Type 1 Diabetes Mellitus and Celiac Disease: Implications in Treatment.

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Interplay between Type 1 Diabetes Mellitus and Celiac Disease: Implications in Treatment.

Dig Dis. 2018;36(6):399-408

Authors: Kaur N, Bhadada SK, Minz RW, Dayal D, Kochhar R

Abstract
BACKGROUND: A complex interplay between genetic and environmental factors contributes to disease etiology of most of the autoimmune disorders. Type 1 diabetes mellitus (T1DM) and celiac disease (CD) are polygenic autoimmune diseases that have high propensity to coexist due to shared etiological factors like genetics and clinico-pathological overlaps.
SUMMARY: The mean prevalence rate for coexistence of these diseases is 8%, and this value is a gross underestimation as reported from biopsy-proven symptomatic cases. The prevalence rate will rise when studies will excavate bottom layers of the "celiac iceberg" to detect potential and silent celiac cases. The concomitant presence of both these disorders is a complex situation immunologically as well as clinically. There is an accentuated breakdown of tolerance and proinflammatory cytokine storm that leads to the progression of organ-specific autoimmunity to systemic. No immunomodulating drugs are advocated as exogenous insulin supplementation and gluten exclusion are recommended for T1DM and CD respectively. Nevertheless, these pose certain challenges to both the clinicians and the patients, as gluten free diet (GFD) has been described to have an impact on glycemic control, bone health, and vascular complications. Also intermittent gluten intake by these patients due to non-compliance with GFD also stimulates the autoreactive immune cells that result in an augmented immune response. Key Messages: Large public health studies are needed to estimate the prevalence of all forms of CD in T1DM patients. Strict global guidelines need to be formulated for the disease management and prognosis, and there is also a need for an extensive research on each front to thoroughly understand the co-occurrence of these diseases.

PMID: 30045024 [PubMed - indexed for MEDLINE]

A Randomized, Placebo-Controlled, Pilot Clinical Trial to Evaluate the Effect of Supplementation with Prebiotic Synergy 1 on Iron Homeostasis in Children and Adolescents with Celiac Disease Treated with a Gluten-Free Diet.

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A Randomized, Placebo-Controlled, Pilot Clinical Trial to Evaluate the Effect of Supplementation with Prebiotic Synergy 1 on Iron Homeostasis in Children and Adolescents with Celiac Disease Treated with a Gluten-Free Diet.

Nutrients. 2018 Nov 21;10(11):

Authors: Feruś K, Drabińska N, Krupa-Kozak U, Jarocka-Cyrta E

Abstract
Iron deficiency anemia (IDA) occurs in 15⁻46% of patients with celiac disease (CD), and in some cases, it may be its only manifestation. Studies in animal models have shown that prebiotics, including inulin, may help to increase intestinal absorption of iron. The aim of this study was to evaluate the effect of a prebiotic, oligofructose-enriched inulin (Synergy 1), on iron homeostasis in non-anemic children and adolescents with celiac disease (CD) in association with a gluten-free diet (GFD). Thirty-four CD patients (4⁻18 years old) were randomized into two groups receiving Synergy 1 (10 g/day) or a placebo (maltodextrin) for three months. Before and after intervention, blood samples were collected from all patients for assessment of blood morphology, biochemical parameters and serum hepcidin concentration. We found that serum hepcidin concentration after the intervention was significantly decreased by 60.9% (p = 0.046) in the Synergy 1 group, whereas no significant difference was observed in the placebo group. No differences in morphological and biochemical blood parameters (including ferritin, hemoglobin and C-reactive protein (CRP)) were observed after intervention in either group. Given that hepcidin decrease may improve intestinal iron absorption, these results warrant further investigation in a larger cohort and especially in patients with IDA.

PMID: 30469412 [PubMed - in process]

Inhibitory effects of Clematis orientalis aqueous ethanol extract and fractions on inflammatory markers in complete Freund's adjuvant-induced arthritis in Sprague-Dawley rats.

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Inhibitory effects of Clematis orientalis aqueous ethanol extract and fractions on inflammatory markers in complete Freund's adjuvant-induced arthritis in Sprague-Dawley rats.

Inflammopharmacology. 2018 Nov 16;:

Authors: Hasan UH, Alamgeer, Shahzad M, Jahan S, Niazi ZR, Bukhari IA, Assiri AM, Riaz H

Abstract
Clematis orientalis Linn has long been used as ethnopharmacy for the treatment of arthritis. This study is intended to evaluate the curative efficacy of Clematis orientalis in treating polyarthritis in rats. Aqueous ethanolic extract and fractions (hexane, butanol and aqueous) were administered orally at 200 mg/kg for 28 days after CFA immunization. Paw swelling, paw diameter, arthritic score, body weight, hematological parameters, radiographic and histological analysis of ankle joints were evaluated. Moreover, levels of various inflammatory markers through RT-PCR and ELISA were measured. DPPH and reducing power assays were used to appraise antioxidant capacity. Qualitative phytochemical analysis, determination of total phenolic and flavonoid contents were also carried out. Aqueous ethanolic extract and fractions significantly (p < 0.001) reduced paw volume, paw thickness and arthritic score and considerably prevented decrease in body weight along with anomalous alterations in hematological parameters in comparison with arthritic control. X-ray and histological examination revealed no significant structural changes in ankle joints of treated rats. Expression levels of IL-1β, TNF-α, IL-6, COX-2 and NF-Kβ were significantly (p < 0.05-0.001) suppressed as well as noteworthy increase in the levels of IL-4 and IL-10 among treated animals has been detected. Overproduction of TNF-α and PGE2 was substantially prevented in animals given different treatments. Aqueous ethanol extract and its fractions demonstrated significant and concentration-dependent antioxidant potential. In general, among fractions aqueous fraction exhibited a greater anti-arthritic effect. Phytochemical analysis of aqueous fraction confirmed the presence of flavonoids and glycosides, 215.29 mgGAE/ml phenolic content and 633.03 μgQE/ml flavonoid content. Thus, we suggest Clematis orientalis as a potent strategy for the treatment of rheumatoid arthritis.

PMID: 30446927 [PubMed - as supplied by publisher]

Beneficial Effect of Oligofructose-Enriched Inulin on Vitamin D and E Status in Children with Celiac Disease on a Long-Term Gluten-Free Diet: A Preliminary Randomized, Placebo-Controlled Nutritional Intervention Study.

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Beneficial Effect of Oligofructose-Enriched Inulin on Vitamin D and E Status in Children with Celiac Disease on a Long-Term Gluten-Free Diet: A Preliminary Randomized, Placebo-Controlled Nutritional Intervention Study.

Nutrients. 2018 Nov 15;10(11):

Authors: Drabińska N, Krupa-Kozak U, Abramowicz P, Jarocka-Cyrta E

Abstract
Prebiotics have been shown to improve absorption of some nutrients, including vitamins. This pilot study evaluated the effect of the prebiotic oligofructose-enriched inulin (Synergy 1) on fat-soluble vitamins status, parathormone, and calcium-related elements in pediatric celiac disease (CD) patients (n = 34) on a strict gluten-free diet (GFD). Participants were randomized into a group receiving 10 g of Synergy 1 or placebo (maltodextrin) together with a GFD. At baseline and after 3 months of intervention, 25-hydroxyvitamin D [25(OH)D], parathormone, vitamin E and A, calcium, phosphate, magnesium, total protein, and albumin were determined. Concentration of 25(OH)D increased significantly (p < 0.05) by 42% in CD patients receiving Synergy 1 in GFD, whereas no change was observed in placebo. Vitamin D status reached an optimal level in 46% of patients receiving Synergy 1. No significant difference in parathormone, calcium, and phosphate levels was observed. Concentration of vitamin E increased significantly (p < 0.05) by 19% in patients receiving Synergy 1, but not in the placebo. Vitamin A levels were not changed. Supplementation of GFD with Synergy 1 improved vitamin D and vitamin E status in children and adolescents with CD and could be considered a novel complementary method of management of fat-soluble vitamins deficiency in pediatric CD patients.

PMID: 30445682 [PubMed - in process]

Tissue transglutaminase autoantibodies in children with newly diagnosed type 1 diabetes are related to human leukocyte antigen but not to islet autoantibodies: A Swedish nationwide prospective population-based cohort study.

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Tissue transglutaminase autoantibodies in children with newly diagnosed type 1 diabetes are related to human leukocyte antigen but not to islet autoantibodies: A Swedish nationwide prospective population-based cohort study.

Autoimmunity. 2018 Nov 16;:1-7

Authors: Cerqueiro Bybrant M, Grahnquist L, Örtqvist E, Andersson C, Forsander G, Elding Larsson H, Lernmark Å, Ludvigsson J, Marcus C, Carlsson A, Ivarsson SA

Abstract
OBJECTIVES: This study explored the association between tissue transglutaminase autoantibody (tTGA), high-risk human leucocyte antigen (HLA) genotypes and islet autoantibodies in children with newly diagnosed type 1 diabetes (T1D).
PATIENTS AND METHODS: Dried blood spots and serum samples were taken at diagnosis from children <18 years of age participating in Better Diabetes Diagnosis (BDD), a Swedish nationwide prospective cohort study of children newly diagnosed with T1D. We analyzed tTGA, high-risk HLA DQ2 and DQ8 (DQX is neither DQ2 nor DQ8) and islet auto-antibodies (GADA, IA-2A, IAA, and three variants of Zinc transporter; ZnT8W, ZnT8R, and ZnT8QA).
RESULTS: Out of 2705 children diagnosed with T1D, 85 (3.1%) had positive tTGA and 63 (2.3%) had borderline values. The prevalence of tTGA was higher in children with the HLA genotypes DQ2/2, DQ2/X or DQ2/8 compared to those with DQ8/8 or DQ8/X (p = .00001) and those with DQX/X (p ≤ .00001). No significant differences were found in relation to islet autoantibodies or age at diagnosis, but the presence of tTGA was more common in girls than in boys (p = .018).
CONCLUSION: tTGA at T1D diagnosis (both positive and borderline values 5.4%) was higher in girls and in children homozygous for DQ2/2, followed by children heterozygous for DQ2. Only children with DQ2 and/or DQ8 had tTGA. HLA typing at the diagnosis of T1D can help to identify those without risk for CD.

PMID: 30444426 [PubMed - as supplied by publisher]

Autism Spectrum Disorders and Celiac Disease: Is there an Association?

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Autism Spectrum Disorders and Celiac Disease: Is there an Association?

Indian Pediatr. 2018 Oct 15;55(10):912-914

Authors: Juneja M, Venkatakrishnan A, Kapoor S, Jain R

Abstract
We included 150 children aged 2-12 years with Autism Spectrum Disorders and normal serum total IgA levels, and screened them for celiac disease using anti-tissue transglutaminase IgA levels. All the children were screen negative, suggesting lack of positive association between Autism Spectrum Disorders and Celiac disease.

PMID: 30426961 [PubMed - in process]

Therapeutic Microbiology: The Role of Bifidobacterium breve as Food Supplement for the Prevention/Treatment of Paediatric Diseases.

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Therapeutic Microbiology: The Role of Bifidobacterium breve as Food Supplement for the Prevention/Treatment of Paediatric Diseases.

Nutrients. 2018 Nov 10;10(11):

Authors: Bozzi Cionci N, Baffoni L, Gaggìa F, Di Gioia D

Abstract
The human intestinal microbiota, establishing a symbiotic relationship with the host, plays a significant role for human health. It is also well known that a disease status is frequently characterized by a dysbiotic condition of the gut microbiota. A probiotic treatment can represent an alternative therapy for enteric disorders and human pathologies not apparently linked to the gastrointestinal tract. Among bifidobacteria, strains of the species Bifidobacterium breve are widely used in paediatrics. B. breve is the dominant species in the gut of breast-fed infants and it has also been isolated from human milk. It has antimicrobial activity against human pathogens, it does not possess transmissible antibiotic resistance traits, it is not cytotoxic and it has immuno-stimulating abilities. This review describes the applications of B. breve strains mainly for the prevention/treatment of paediatric pathologies. The target pathologies range from widespread gut diseases, including diarrhoea and infant colics, to celiac disease, obesity, allergic and neurological disorders. Moreover, B. breve strains are used for the prevention of side infections in preterm newborns and during antibiotic treatments or chemotherapy. With this documentation, we hope to increase knowledge on this species to boost the interest in the emerging discipline known as "therapeutic microbiology".

PMID: 30423810 [PubMed - in process]

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