Celiac Disease Children Research Articles

Guideline adherence and clinical relevance of laboratory investigations during follow-up in paediatric coeliac disease: A Dutch single-centre cohort study.

Dutch national guidelines on follow-up of paediatric celiac disease (CD) are available. The primary aim was to evaluate guideline adherence by paediatricians during follow-up. The secondary aim was to determine the clinical relevance and diagnostic yield of routine laboratory tests suggested by these guidelines. A retrospective, single-centre, cohort study was performed in paediatric CD patients who visited Tergooi Hospital, the Netherlands, between January 2017 and December 2019, with follow-up of at least twelve months after diagnosis. We analysed guideline adherence, number of outpatient visits and all laboratory data. We included 91 CD children with a median follow-up of 4.0years (range 1-16years) and 162 follow-up visits. Strict adherence amongst paediatricians during follow-up was 8.0% (13/162 cases). A total of 1570laboratory tests were performed of which 45.4% (713/1570) was in strict compliance with the Dutch national guidelines. Clinically relevant deviations were observed in 5.3% of requested laboratory tests. Strict guideless adherence amongst paediatricians in follow-up of paediatric CD was low and the clinical relevance of the suggested routine laboratory tests is limited. This underlines the increasing notion that evidence-based guidelines on follow-up of CD are warranted.

Gene Expression of NLRP3 Inflammasome in Celiac Disease of Iraqi Children

Celiac disease (CD) is an autoimmune disorder characterized by chronic inflammation that essentially affects the small intestine and is caused by eating gluten-containing foods. This study sought to determine gene expression of NLRP3 Inflammasome in peripheral blood of Iraqi CD children using quantitative real-time PCR (qRT-PCR) assay. Thirty children with CD (12 males and 18 females) were enrolled in the study and their age range was 3-15 years. The diagnosis of the disease was confirmed by serological examinations and intestinal endoscopy. A control sample of 20 age-matched healthy children was also included. The children were stratified for age, gender, body max index (BMI), histological findings, and marsh classification. Further, the sera were examined for IgA anti-tissue transglutaminase (tTG) antibody, IgA anti-gliadin antibody, and interleukin-1 beta (IL-1β). Based on Marsh classification, the results revealed that the majority of patients (70%) had partial villous atrophy (Marsh Ш 3A), while children with subtotal and total villous atrophy (Marsh III: 3B/3C) were presented with a lower frequency (30.0%). Neither Marsh I nor Marsh II has been observed among the patients studied. Serum levels of anti-tTG and anti-gliadin IgA antibodies were significantly higher in CD children than in control children (73.8 and 31.8 vs. 0.8 U//ml, respectively; p < 0.001). Conversely, IL-1β serum level was decreased in CD children but the difference was not significant (35.5vs. 53.4 pg/ml; p = 0.285). In the case of NLRP3 inflammasome, the Relative Fold Change method (2-∆∆Ct) was used to assess the gene expression. The results revealed that the expression of NLRP3 inflammasome was decreased by 0.594 fold in CD children. In conclusion, the NLRP3 inflammasome was down-regulated in the present sample of CD children, and it was accompanied by a decreased serum level of IL-1β.

Evaluation of Aortic Elasticity in Children with Celiac Disease Compared with Controls

Background Celiac disease (CD) is a lifelong, chronic and immune-mediated disorder. Recent studies have turned on a new light on the importance of inflammation in the pathogenesis of arterial stiffness. The aim of this study was to evaluate arterial stiffness in children with celiac disease compared with controls. Materials and Methods: In this case-control study, fifty children aged from 3.5 to 18 year- old with celiac compared with 50 age and sex-matched controls. The study performed in Ali Asghar pediatric hospital in Zahedan city, Iran during the year 2019. Echocardiography, aortic elasticity, blood pressure, tissue transglutaminase IgA (tTG-IgA), and anthropomorphic parameters were measured. Arterial stiffness indices determined using 2D and Doppler echocardiography. Data were analyzed using SPSS software version 20.0. Results: In all and CD children, 51% and 56% were girls, respectively. Systolic and diastolic blood pressure were lower in patients (p <0.001). Aortic diameter in diastole was lower in patients significantly (p <0.001). Aortic strain (<0.001), PSEM (<0.001), AD (<0.001), and ASI (p <0.001) were different between celiac patients and controls. Tissue transglutaminase IgA (tTG-IgA) was changed significantly with Marsh classification (p <0.001); tTG-IgA was correlated with strain (r= 0.417, p=0.003), and AD (r= 0.282, p=0.047) before age control when the trends did not change after age control for AD (r=0.241, p=0.096). LVMI was correlated with strain (r=-0309, p=0.029), PSEM (r=0.322, p=0.023), and AD (r=0.326, p=0.021) before controlling age when after age control this significant correlation omitted. Conclusion Concluded that aortic elastic risk is higher in celiac children when is free of modified marsh classification. Most of the aortic elastic parameters had significant correlation with changes of tTG-IgA antibody in children with celiac disease.

Influence of Mediterranean Diet Adherence and Physical Activity on Bone Health in Celiac Children on a Gluten-Free Diet.

We aimed to assess the influence of the Mediterranean Diet adherence and physical activity (PA) on body composition, with a particular focus on bone health, in young patients with celiac disease (CD). The CD group (n = 59) included children with CD with a long (>18 months, n = 41) or recent (<18 months, n = 18) adherence to a gluten-free diet (GFD). The non-celiac group (n = 40) included non-celiac children. After adjusting for potential confounders, the CD group showed lower body weight (p = 0.034), lean mass (p = 0.003), bone mineral content (p = 0.006), and bone Z-score (p = 0.036) than non-celiac children, even when the model was further adjusted for adherence to a GFD for at least 18 months. Among CD children, spending greater time in vigorous physical activity was associated with higher lean mass (p = 0.020) and bone mineral density with evidence of statistical significance (p = 0.078) regardless of the time they followed a GFD. In addition, a greater Mediterranean Diet adherence was associated with a higher bone Z-score (p = 0.020). Moreover, lean mass was strongly associated with bone mineral density and independently explained 12% of its variability (p < 0.001). These findings suggest the importance of correctly monitoring lifestyle in children with CD regarding dietary habits and PA levels to improve lean mass and, consequently, bone quality in this population.

RED BLOOD INDICES, PLATELET COUNT AND TRANSFERRIN LEVELS IN CELIAC PATIENTS WITH AND WITHOUT TYPE 1 DIABETES MELLITUS IN HYDERABAD, SINDH, PAKISTAN

OBJECTIVE: To analyze the hematological manifestations among celiac disease &nbsp;(CD) and CD with type-1 diabetes mellitus &nbsp;(T1DM) children to aid in differential diagnosis and management of disease. METHODS: This study was conducted at Institute of Biotechnology and Genetic Engineering, University of Sindh, Jamshoro, Pakistan.&nbsp; CD pediatric patients were diagnosed through serological or intestinal biopsy. The individuals were divided into 5 groups (35 each); Control (A), diagnosed cases of CD (B), individuals affected with celiac-like indications (C), T1DM patients with celiac-like symptoms (D) and T1DM patients (E). RESULTS: &nbsp;Mean age of 175 participants was 9.5±1.2 years. Mean hemoglobin level (mg/dl) was 9.1±1.1, 9.03±1.4, 8.64±1.2 and 11.7±1.3 in group-B, group-C, group-D and group-E respectively as compared to 13.02±1.5 in Group-A (p&lt;0.001). Mean corpuscular volume (MCV) [fl] was 64.1±5.4, 68.5±7.8, 57.6±6.0 and 69.4±4.4 in group-B, group-C, group-D and group-E respectively as compared to 84.4±7.3 in Group-A (p&lt;0.001). Mean corpuscular hemoglobin (MCH) [group-B: 24.1pg, group-C: 25.5pg, group-D: 24.6pg] and mean corpuscular hemoglobin concentration (MCHC) [group-B: 29.3 g/dl, group-C: 277.9 g/dl, group-D: 31.5 g/dl] were decreased among all celiac affected cases. For group-E the hemoglobin, MCV and MCHC were in the normal ranges. Platelet Count (cells/ul) was 689±178x103, 702±141x103, 518±124x103 and 529±101x103 in group-B, group-C, group-D &amp; group-E respectively as compared to 326±98x103 in group A (p&lt;0.01). Mean Transferrin levels (mg/dl) were 411.5±24.8; 387.7±22.4; 406.4±21.4 &amp; 368.8±22.0 in group-B, group-C, group-D and group-E and 271.1±39.1 in group-A (p&lt;0.01). CONCLUSION: Hematological anomalies; like anemia and thrombocytosis are frequently present in mismanaged and late diagnosed CD children.

FODMAP intake in children with coeliac disease influences diet quality and health-related quality of life and has no impact on gastrointestinal symptoms

Children with coeliac disease (CD) following the gluten-free diet may experience ongoing gastrointestinal symptoms despite strict adherence. The study objective was to evaluate the association between foods high in fermentable oligo/di/monosaccharides, and polyols (FODMAP) and gastrointestinal symptoms, and the potential implications to diet quality and health-related quality of life in CD children. Dietary intake was studied in age-sex matched children 5–18 years (CD, n = 46; non-coeliac mild chronic gastrointestinal complaints [GIC], n = 46; healthy controls [HC], n = 46). CD children consumed fewer foods high in FODMAPs compared to GIC and HC (p < .0001). FODMAP intake was not related to gastrointestinal symptoms in CD children (p > 0.05) but was positively associated with child health-related quality of life (p < 0.05). FODMAP intake from fruits and vegetables was positively associated with diet adequacy and total diet quality in CD children (p < 0.05). FODMAP intake may influence diet quality and health-related quality of life but has no impact on gastrointestinal symptoms in CD children.

Clinical Characteristics of Children With Celiac Disease Not Responding to Hepatitis B Vaccination in India.

This study was undertaken to assess the immune response to HBV vaccine in CD children and to explore the possible factors affecting the immune response. The study population consisted of 3 groups-50 newly diagnosed CD children (group 1), 50 previously diagnosed CD children who were on gluten free diet (GFD) >3 months (group 2), and 100 age and gender matched healthy controls (group 3). The patient characteristics were recorded, and the blood samples were analyzed for HBsAg and anti-HBs titers. The nonresponders were given a booster dose of HBV vaccine and reevaluated after 6 weeks. Positive anti-HBs response was found in 46% in newly diagnosed CD children, 60% in CD children on GFD, and 83% in healthy controls (P < 0.001). The immune response to HBV vaccine in CD children was inferior to that in healthy children (53% vs 83%, P < 0.001). The immune response was found to be significantly affected by age at diagnosis, delay in diagnosis, type of presentation, and compliance to GFD. 44 out of 45 (97.77%) nonresponders from CD group seroconverted after a single booster dose. Early diagnosis and good compliance to GFD may improve the immune response to HBV vaccine in CD children. Single additional booster dose is sufficient to attain optimal immune response.

Illness Identity in Adolescents With Celiac Disease.

The aim was to examine the reliability and validity of the Illness Identity Questionnaire (IIQ) among adolescents with celiac disease (CD), to describe their illness identity characteristics, and to examine relationships between illness identity and self-reported participation in food-related activities and quality of life. Adolescents with CD (n = 91) were recruited for this cross-sectional study via social media interest groups. Participants completed online questionnaires: the IIQ, the CD Children's Activities Chart (CD-Chart), and the Pediatric Quality of Life Inventory (PedsQL). Internal reliability was established for IIQ items (α = 0.87) and for its 4 components (α = 0.75--0.90). The positive components (acceptance, enrichment) significantly differed from the negative components (rejection, engulfment), t(90) = 11.45, P < 0.001, d = 1.98. Feelings were more positive (M = 3.48, SD = 0.67) than negative (M = 2.06, SD = 0.76). The total IIQ was positively associated with the CD-Chart amount of activities (r = 0.30, P < 0.01) and enjoyment (r = 0.34, P < 0.001) and with the PedsQL social scale (r = 0.53, P < 0.001). The IIQ established acceptable reliability and validity. In all, the adolescents with CD exhibited an illness identity profile that was more positive and adaptive than negative. The IIQ can contribute to understanding the developmental status of illness identity during the critical transition process from adolescence to adulthood.

Association between Elevated TGA-IgA Titers and Older Age at Diagnosis with Absence of HBV Seroconversion in Celiac Children.

Patients with celiac disease can have a low rate of protective hepatitis B (HBV) antibody titers after vaccination. We aimed to evaluate the HBV seroconversion in celiac disease (CD) children at the time of diagnosis as well as to identify the presence of possible predictive factors. Celiac disease children were prospectively enrolled and tested for antibodies against the S protein of HBV (HBsAg) at time of diagnosis between January 2009 and February 2020. Based on the serologic response to the vaccine, “responders” and “non-responders” were identified. Statistical analysis has been performed through R statistical software (3.5.1 version, R core Team) Of 96 CD children evaluated, 41.7% (n = 40) showed non-protective or absent antibody titers against HBV. Elevated IgA-antibodies against transglutaminase 2 (TGA-IgA) values and older age at diagnosis were associated with an absent seroconversion to HBV vaccine, while presenting symptoms were not significant. An elevated prevalence of absent seroconversion to HBV vaccine exists in this cohort of CD patients at the time of disease diagnosis. Elevated TGA-IgA titers and older age at diagnosis seem to negatively predict seroconversion. Further studies are needed to identify the real profile of “non-responders”, aiming to organize surveillance and eventual revaccination strategy.

Quantification of Accidental Gluten Contamination in the Diet of Children with Treated Celiac Disease.

A strict gluten-free diet is extremely difficult to maintain. Protracted ingestion of gluten traces (>10 mg/day) is sufficient to cause significant damage in the architecture of the small intestinal mucosa in patients on treatment for celiac disease. The aim of this study was to directly measure the level of contaminating gluten in the daily diet of celiac children following a gluten-free diet. From April 2019 to December 2019, celiac disease children (2–18 years old) on a gluten-free diet for ≥6 months were offered to participate in this prospective-observational study. Patients and their caregivers were invited to provide a representative portion (about 10 g) of all meals consumed during a 24-h period. Participants were requested to weigh all ingested food and report items in a 24-h food diary. The gluten content was quantified by the R5 sandwich enzyme-linked immunosorbent assay method. Sixty-nine children completed the protocol. Overall, 12/448 (2.7%) food samples contained detectable amounts of gluten; of them, 11 contained 5–20 ppm and 1 >20 ppm. The 12 contaminated food samples belonged to 5/69 enrolled patients. In these 5 children, the daily gluten intake was well below the safety threshold of 10 mg/day. The present findings suggest that in a country characterized by high celiac disease awareness, the daily unintended exposure to gluten of treated celiac children on regular follow-up is very low; reassuringly, the presence of gluten traces did not lead to exceed the tolerable threshold of 10 mg/day of gluten intake in the gluten-free diet.

Influence of Ultra-Processed Foods Consumption on Redox Status and Inflammatory Signaling in Young Celiac Patients.

The current study was designed to assess the influence of consumption of ultra-processed (UPF) on oxidative/antioxidant balance and evoked inflammatory signaling in young patients with celiac disease (CD). The study included 85 children. The celiac group (n = 53) included children with CD with a long (>18 months, n = 17) or recent (<18 months, n = 36) adherence to a gluten-free diet (GFD). The control group (n = 32) included healthy children with a significantly lower consumption of UPF compared to the CD group, both expressed as kcal/day (p = 0.043) and as percentage of daily energy intake (p = 0.023). Among children with CD, the group with the lowest consumption of UPF (below the 50% of daily energy intake) had a greater Mediterranean diet (MD) adherence and higher moderate physical activity levels. In addition, CD children with the lowest consumption of UPF had healthier redox (lower soluble superoxide dismutase-1 and 15-F2t-isoprostanes) and inflammatory profiles (lower macrophage inflammatory protein-1α) compared to the group with the highest consumption of UPF (all, p < 0.05) regardless of the time on a GFD. These findings highlight the importance of a correct monitoring of the GFD. An unbalanced GFD with high consumption of UPF and an unhealthy pattern with less physical activity and worse adherence to MD results in a worse inflammatory profile, which could act as a parallel pathway that could have important consequences on the pathophysiology of the disease.

Quality of life of families with celiac disease children in Eastern Province of Saudi Arabia

Objectives: The prevalence of Celiac Disease (CD) is increasing worldwide, and the kingdom of Saudi Arabia reports the highest seroprevalence rate. A strict Gluten-Free Diet (GFD) for lifetime is the only therapy to CD patients. It has been demonstrated that childhood CD negatively affects the health of parents. On the other hand, the emotional and social wellbeing of the parents has a great impact on the Quality Of Life (QOL) of CD children. However, limited literatures are available on the QOL of parents of CD children. This study aims to evaluate the QOL of families of celiac disease children on GFD treatment and identify modifiable risk factors for poor QOL. Methods: A total of 73 children with celiac disease living in different cities of the eastern province of the kingdom of Saudi Arabia were included in this descriptive, cross-sectional study. A modified version of the celiac disease-specific instrument measuring the QOL was used. Data analyses were done using descriptive statistics, correlation coefficient test and the Fisher’s exact test. Results: The mean QOL score was found to be 65.8 and the median was 64.0. Very few (5.48%) parents perceived their QOL to be good, while majority of them (78.08%) considered it as moderate; and the remaining parents (16.44%) regarded it as poor. Conclusions: We found that small-sized families, with young and educated mothers have a better QOL than others. Most of the emotional and psychosocial elements of QOL were related to the difficulties in availability of GFD in daily life.

Oral manifestations of celiac disease in French children

Celiac disease (CD) is an immune-mediated systemic disorder caused by ingestion of the gluten found in wheat, rye, and barley. The currently estimated prevalence in children is about 1%. CD is a chronic enteropathy with gastrointestinal manifestations including diarrhea, abdominal distension and weight loss, but extra-intestinal features are increasingly being reported. Dental and oral manifestations such as dental enamel defects (ED), delay in dental eruption, and recurrent aphthous stomatitis (RAS) are well-recognized manifestations of CD. The aim of this study was to compare the frequency of oral manifestations (ED, RAS and delay in dental eruption) on deciduous and permanent teeth between children with CD and a control population. An oral examination was performed on 28 CD children and 59 control children. All children were younger than 12 years old and had deciduous or mixed dentition. CD children had significantly more ED and RAS than the control group (67.9% vs. 33.9% P=0.004 and 50.0% vs. 21.8% P=0.011, respectively). No delay in dental eruption was observed in CD children. ED were mainly grade I and II of Aine's classification (color defects and slight structural defects). ED were more often seen on CD children's deciduous teeth than on permanent teeth (57.1% and 13.6%, respectively; P<0.001). The main teeth affected by ED are the second molar and canines of the deciduous teeth, and the first molar, central incisor, and lateral incisors of the permanent teeth. RAS and ED that were symmetrical in all quadrants and occurred firstly in teeth that mineralize during the first year of life both seem to be signs of CD. Thus, more information for dentists and pediatricians on these oral manifestations should help improve detection of CD.

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Distribution of HLA-DQ risk genotypes for celiac disease in Ethiopian children.

Most patients with celiac disease are positive for either HLA‐DQA1*05:01‐DQB1*02 (DQ2.5) or DQA1*03:01‐DQB1*03:02 (DQ8). Remaining few patients are usually DQA1*02:01‐DQB1*02 (DQ2.2) carriers. Screenings of populations with high frequencies of these HLA‐DQA1‐DQB1 haplotypes report a 1% to 3% celiac disease prevalence. The aim was to determine the prevalence of HLA‐DQ risk haplotypes for celiac disease in Ethiopian children. Dried blood spots collected from 1193 children from the Oromia regional state of Ethiopia were genotyped for HLA‐DQA1 and DQB1 genotyping using an asymmetric polymerase chain reaction (PCR) and a subsequent hybridization of allele‐specific probes. As references, 2000 previously HLA‐genotyped children randomly selected from the general population in Sweden were included. DQ2.2 was the most common haplotype and found in 15.3% of Ethiopian children, which was higher compared with 6.7% of Swedish references (P < .0001). Opposed to this finding, DQ2.5 and DQ8 occurred in 9.7% and 6.8% of Ethiopian children, which were less frequent compared with 12.8% and 13.1% of Swedish references, respectively (P < .0001). The DQ2.5‐trans genotype encoded by DQA1*05‐DQB1*03:01 in combination with DQ2.2 occurred in 3.6% of Ethiopian children, which was higher compared with 1.3% of Swedish references (P < .0001). However, when children with moderate high to very high‐risk HLA genotypes were grouped together, there was no difference between Ethiopian children and Swedish references (27.4% vs 29.0%) (P = .3504). The frequency of HLA risk haplotypes for celiac disease is very similar in Ethiopian and Swedish children. This finding of importance will be useful in future screening of children for celiac disease in Ethiopia.

Analysis of gluten immunogenic peptides in feces to assess adherence to the gluten-free diet in pediatric celiac patients.

In celiac disease (CD) there is a need for precise and non-invasive tools to assess dietary compliance to the gluten-free diet (GFD). Our aim is to evaluate the efficacy of the detection of gluten immunogenic peptides (GIP) in feces, to monitor in real life, the adherence to GFD in pediatric patients with CD. A cross-sectional, prospective study was conducted. Fecal samples from CD children were analyzed by a rapid immunochromatographic (IC) test and by an ELISA method, both based on the antigliadin 33-mer monoclonal antibody. Group 1 comprises 43 children on a GFD. According to the food records (FR), 39/43 patients were compliant with the GFD and gluten consumption was recorded in 4. GIP were detected in 15/43 individuals by the ELISA method and also in 7 by IC strips. Group 2: comprise 18 children at CD diagnosis; GIP levels decreased over time (p<0.001) in a non-linear way (p=0.028) after starting a GFD and were below the detection limit on the third day in most individuals. GIP were detected, both by ELISA and by IC strips, in CD patients on a GFD, in which no consumption of gluten had been registered on the FR, confirming GIP detection to be superior to FR discovering involuntary transgressions. Despite a positive correlation between the amount of gluten intake and the concentration of GIP in feces, the interindividual variations observed suggest gastrointestinal factors influencing GIP recovery need to be further investigated.

ESPGHAN 'biopsy-sparing' guidelines for celiac disease in children with low antitransglutaminase during COVID-19.

Recent guidelines for celiac disease have allowed a biopsy-free approach in endomysial antibodies (EMAs) positive children with high antitransglutaminase (TGA-IgA) titer [>10 time upper limit of normal (ULN)]. Esophagogastroduodenoscopy is still necessary for diagnosis in children with lower title. Because elective pediatric endoscopy has been substantially shouted down during coronavirus disease (COVID-19) pandemic, many children remained undiagnosed - and therefore untreated - for a long time. We aimed to analyze the feasibility and accuracy of a biopsy-free approach in suspected celiac disease children with TGA-IgA values <10 ULN to facilitate the diagnostic process by avoiding endoscopy. In this study cohort, we retrospectively analyzed all biopsy-confirmed diagnosis of celiac disease in our center (between 2014 and 2019). The positive predictive value (PPV) of TGA-IgA titers between 5 and 10 ULN and positive EMA in diagnosing celiac disease were determined. Mucosal atrophy and resolution of symptoms after gluten-free diet (GFD) were considered to confirm initial diagnosis. Of 430 celiac disease patients (F: 274; mean age 7.54 years) diagnosed by endoscopy, 84 (F: 46; mean age 8 years) with TGA-IgA between 5 and 10 ULN and positive EMA were identified. The PPV of TGA-IgA between 5 and 10 ULN and positive EMA was 0.93 (95% confidence interval 0.90-0.96). All these children had a symptom resolution and antibodies normalization after GFD. During the COVID-19 outbreak, a temporarily reduction of the TGA-IgA threshold for biopsy-sparing approach seems feasible in EMA positive children with TGA-IgA between 5 and 10 ULN.

Alterations in Intestinal Microbiota of Children With Celiac Disease at the Time of Diagnosis and on a Gluten-free Diet

Background And AimsIt is not clear whether alterations in the intestinal microbiota of children with celiac disease (CD) cause the disease or are a result of disease and/or its treatment with a gluten-free diet (GFD).MethodsWe obtained 167 fecal samples from 141 children (20 with new-onset CD, 45 treated with a GFD, 57 healthy children, and 19 unaffected siblings of children with CD) in Glasgow, Scotland. Samples were analyzed by 16S ribosomal RNA sequencing, and diet-related metabolites were measured by gas chromatography. We obtained fecal samples from 13 children with new-onset CD after 6 and 12 months on a GFD. Relationships between microbiota with diet composition, gastrointestinal function, and biomarkers of GFD compliance were explored.ResultsMicrobiota α diversity did not differ among groups. Microbial dysbiosis was not observed in children with new-onset CD. In contrast, 2.8% (Bray-Curtis dissimilarity index, P = .025) and 2.5% (UniFrac distances, P = .027) of the variation in microbiota composition could be explained by the GFD. Between 3% and 5% of all taxa differed among all group comparisons. Eleven distinctive operational taxonomic units composed a microbe signature specific to CD with high diagnostic probability. Most operational taxonomic units that differed between patients on a GFD with new-onset CD vs healthy children were associated with nutrient and food group intake (from 75% to 94%) and with biomarkers of gluten ingestion. Fecal levels of butyrate and ammonia decreased during the GFD.ConclusionsAlthough several alterations in the intestinal microbiota of children with established CD appear to be effects of a GFD, specific bacteria were found to be distinct biomarkers of CD. Studies are needed to determine whether these bacteria contribute to pathogenesis of CD.

The Role of Cannabinoid Receptor Type 2 in the Bone Loss Associated With Pediatric Celiac Disease.

In this study, we investigated the role of the cannabinoid receptor type 2 (CB2) in the bone loss associated with celiac disease (CD) evaluating the effect of its pharmacological modulation on osteoclast activity. We previously demonstrated a significant association between the CB2 Q63R variant and CD, suggesting it as a possible disease biomarker. Moreover, CB2 stimulation is beneficial for reducing osteoclast activity in several bone pathologic conditions. In vitro osteoclasts (OCs) were differentiated from peripheral blood mononuclear cells of healthy donors, CD children at diagnosis and after 1 year of gluten-free diet (GFD) and characterized by real-time PCR and western blot for the expression of CB2 and specific osteoclastic markers, TRAP and Cathepsin K. TRAP assay and Bone Resorption assay were performed to evaluate osteoclast activity before and after 48 h exposure to CB2 selective drugs (JWH-133 and AM630) and Vitamin D. We found in CD patients an osteoclast hyperactivation and low levels of CB2. CB2 stimulation with JWH-133 agonist is more effective than Vitamin D in reducing osteoclast activity whereas CB2 blockade with AM630 increases osteoclast activation. The anti-osteoporotic effect of JWH-133 decreases when used in co-treatment with vitamin D. GFD reduces osteoclast activity without restore CB2 expression. CB2 could be a molecular marker to predict the risk of bone alterations in CD and a pharmacological target to reduce bone mass loss in patients who need a direct intervention on bone metabolism, in addition to the GFD.

Gut microbiota signatures and clinical manifestations in celiac disease children at onset: a pilot study.

Recent researches have shown an altered gut microbiota in celiac disease (CD) patients compared with healthy controls (HCs). This study aims to evaluate the composition of the microbiota of CD children at onset and the relationship between bacterial abundances and symptoms. Celiac disease patients were consecutively enrolled at a pediatric unit referring for suspected CD. HCs were also included in the study. Stool and duodenal samples were collected and evaluated by a high taxonomic fingerprint microbiota array. Thirty-seven subjects enrolled: 21 CD patients and 16 HCs. Fourteen subjects were male (38%). The mean age was 75months (standard deviation 31.5) for CD patients and 71months (standard deviation 34.9) for HCs. Duodenal microbiota of CD patients showed a dominance of Enterobacteriaceae and subdominance of Bacteroidetes/Streptococcus. Stool microbiota showed a lower abundance of Bacteroides-Prevotella (P=0.013), Akkermansia (P=0.002), and Staphylococcaceae (P=0.001) in CD patients compared with HC. At symptoms level, an increased mean relative abundance of Bacillaceae and Enterobaeriaceae in patients with abdominal pain (P=0.007 and P=0.010) was found. CD patients with diarrhea had reduced mean relative abundance of Clostridium cluster XIVa (P=0.044) and Akkermansia (P=0.033) and an increase in Bacillaceae (P=0.048) and Fusobacterium (P=0.048). Gut microbiota of CD children at disease onset is different from that of HC. Pro-inflammatory microbiota imbalances were associated with CD symptoms. Further studies are needed to assess whether dysbiosis is associated with CD early onset and symptoms.