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The worldwide prevalence of asymptomatic coeliac disease (CD) is increasing, which is in part due to the routine screening of children with risk factors. Both symptomatic and asymptomatic patients with CD are at risk of long-term complications. The objective of this study was to compare the clinical characteristics of asymptomatic and symptomatic children at the time of CD diagnosis. A case-control study was conducted using data from a cohort of 4838 CD patients recruited from 73 centers across Spain between 2011 and 2017. A total of 468 asymptomatic patients (cases) were selected and matched by age and sex with 468 symptomatic patients (controls). Clinical data, including any reported symptoms, as well as serologic, genetic, and histopathologic data were collected. No significant differences were found between the two groups in most clinical variables, nor in the degree of intestinal lesion. However, the asymptomatic patients were taller (height z-score -0.12 (1.06) vs. -0.45 (1.19), p < 0.001) and were less likely to have anti transglutaminase IgA antibodies >= 10 times the upper normal limit (66.2% vs. 758.4%, p = 0.002). Among the 37.1% of asymptomatic patients who were not screened for CD due to the absence of risk factors, only 34% were truly asymptomatic, while the remaining 66% reported non-specific CD-related symptoms. Therefore, expanding CD screening to any child who undergoes a blood test could reduce the burden of care for some children, as many of those considered asymptomatic reported non-specific CD-related symptoms.

Background & Aims: Celiac disease (CeD), an immune-mediated disease with enteropathy triggered by gluten, affects ~1% of the general European population. Currently, there are no biomarkers to predict CeD development. MicroRNAs (miRNAs) are short RNAs involved in post-transcriptional gene regulation, and certain disease- and stage-specific miRNA profiles have been found previously. We aimed to investigate whether circulating miRNAs can predict the development of CeD. Methods: Using next-generation miRNA-sequencing, we determined miRNAs in >200 serum samples from 53 participants of the PreventCD study, of whom 33 developed CeD during follow-up. Following study inclusion at 3 months of age, samples were drawn at predefined ages, diagnosis (first anti-transglutaminase antibody (TGA) positivity or diagnostic biopsy) and after the start of a gluten-free diet (GFD). This allowed identification of circulating miRNAs that are deregulated before TGA positivity. For validation of the biomarkers for CeD and GFD response, two additional cohorts were included in subsequent meta-analyses. Additionally, miRNAs were measured in duodenal biopsies in a case-control cohort. Results: 53 circulating miRNAs were increased (27) or decreased (26) in CeD versus controls. We assessed specific trends in these individual miRNAs in the PreventCD cohort by grouping the pre-diagnostic samples of the CeD patients (all had negative TGA) by how close to seroconversion (first sample positive TGA) the samples were taken. 8/53 miRNAs differed significantly between controls and samples taken <1 year before TGA positivity: miR-21-3p, miR-374a-5p, 144-3p, miR-500a-3p, miR-486-3p let-7d-3p, let-7e-5p and miR-3605-3p. 6/26 downregulated miRNAs reconstituted upon GFD, including miR-150-5p/-3p, whereas no upregulated miRNAs were downregulated upon GFD. 15/53 biomarker candidates also differed between CeD biopsies and controls, with a concordant direction, indicating that these circulating miRNAs migh

AIM: To gather the current evidence and to offer recommendations for follow-up and management.METHODS: The Special Interest Group on Coeliac Diseases of the European Society of Paediatric Gastroenterology Hepatology and Nutrition formulated ten questions considered to be essential for follow-up care. A literature search (January 2010 - March 2020) was performed in PubMed or Medline. Relevant publications were identified and potentially eligible studies were assessed. Statements and recommendations were developed and discussed by all co-authors. Recommendations were voted upon: joint agreement was set as at least 85%.RESULTS: Publications (n=2775) were identified and 164 were included. Using evidence and/or expert opinion, 37 recommendations were formulated on: The need to perform follow-up, its frequency and what should be assessed, how to assess adherence to the gluten-free diet, when to expect catch-up growth, how to treat anaemia, how to approach persistent high serum levels of antibodies against tissue-transglutaminase, the indication to perform biopsies, assessment of quality of life, management of children with unclear diagnosis for which a gluten challenge is indicated, children with associated type 1 diabetes or IgA deficiency, cases of potential coeliac disease, which professionals should perform follow-up, how to improve the communication to patients and their parents/caregivers and transition from paediatric to adult health-care.CONCLUSIONS: We offer recommendations to improve follow-up of children and adolescents with coeliac disease and highlight gaps that should be investigated to further improve management.

Atherosclerosis is a chronic inflammatory disease that is caused by the accumulation of LDL particles in the intima, causing the activation of immune cells and triggering an inflammatory response. LPS is a potent activator of the innate immune response and it can be transported by lipoproteins. Since humans are much more sensitive to LPS than other mammals, and very low amounts of LPS can elicit an immune response, the aim of this study is to characterize the distribution of LPS and its immunogenic portion (3OHFAs) among lipoprotein types of healthy men. We separated lipoprotein fractions by ultracentrifugation and the amount of each 3OHFA was measured by MS in each lipoprotein fraction to calculate LPS concentration. Lipoprotein particle concentration was measured by NMR. LDL and HDL fractions transported the highest concentration of LPS (35.7% and 31.5%, respectively), but VLDL particles carried more LPS molecules per particle (0.55 molecules/particle) than LDL or HDL (p < 0.01). The distribution of LPS and all 3OHFAs among lipoprotein fractions showed high interindividual variability, suggesting that they may be studied as a potential biomarker. This may help understand the role of LPS in atherosclerosis in those cases where the disease cannot be explained by traditional risk factors. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Background and aims: We aimed to describe and characterize the gut microbiota composition and diversity in children with obesity according to their metabolic health status. Methods: Anthropometry, Triglycerides, HDL cholesterol, HOMA-IR, and systolic and diastolic blood pressure (SBP, DBP) were evaluated (and z-score calculated) and faecal samples were collected from 191 children with obesity aged from 8 to 14. All children were classified depending on their cardiometabolic status in either a "metabolically healthy" (MHO; n = 106) or "metabolically unhealthy" (MUO; n = 85) group. Differences in gut microbiota taxonomies and diversity between groups (MUO vs MHO) were analysed. Alpha diversity index was calculated as Chao1 and Simpson's index, and b-diversity was calculated as Adonis Bray-Curtis index. Spearman's correlations and logistic regressions were performed to study the association between cardiometabolic health and the microbiota. Results: Children in the MUO presented significantly lower alpha diversity and richness than those in the MHO group (Chao1 index p = 0.021, Simpson's index p = 0.045, respectively), whereas microbiota bdiversity did not differ by the cardiometabolic health status (Adonis Bray-Curtis, R2 = 0.006; p = 0.155). The MUO group was characterized by lower relative abundances of the genera Christensenellaceae R7 group (MHO:1.42% [0.21-2.94]; MUO:0.47% [0.02-1.60], p < 0.004), and Akkermansia (MHO:0.26% [0.01 -2.19]; MUO:0.01% [0.00-0.36], p < 0.001) and higher relative abundances of Bacteroides (MHO:10.6% [4.64-18.5]; MUO:17.0% [7.18-27.4], p = 0.012) genus. After the adjustment by sex, age, and BMI, higher Akkermansia (OR: 0.86, CI: 0.75-0.97; p = 0.033), Christensenellaceae R7 group (OR: 0.86, 95% CI: 075 -0.98; p = 0.031) and Chao1 index (OR

Background & Aims: Celiac disease (CeD), an immune-mediated disease with enteropathy triggered by gluten, affects ~1% of the general European population. Currently, there are no biomarkers to predict CeD development. MicroRNAs (miRNAs) are short RNAs involved in post-transcriptional gene regulation, and certain disease- and stage-specific miRNA profiles have been found previously. We aimed to investigate whether circulating miRNAs can predict the development of CeD. Methods: Using next-generation miRNA-sequencing, we determined miRNAs in >200 serum samples from 53 participants of the PreventCD study, of whom 33 developed CeD during follow-up. Following study inclusion at 3 months of age, samples were drawn at predefined ages, diagnosis (first anti-transglutaminase antibody (TGA) positivity or diagnostic biopsy) and after the start of a gluten-free diet (GFD). This allowed identification of circulating miRNAs that are deregulated before TGA positivity. For validation of the biomarkers for CeD and GFD response, two additional cohorts were included in subsequent meta-analyses. Additionally, miRNAs were measured in duodenal biopsies in a case-control cohort. Results: 53 circulating miRNAs were increased (27) or decreased (26) in CeD versus controls. We assessed specific trends in these individual miRNAs in the PreventCD cohort by grouping the pre-diagnostic samples of the CeD patients (all had negative TGA) by how close to seroconversion (first sample positive TGA) the samples were taken. 8/53 miRNAs differed significantly between controls and samples taken <1 year before TGA positivity: miR-21-3p, miR-374a-5p, 144-3p, miR-500a-3p, miR-486-3p let-7d-3p, let-7e-5p and miR-3605-3p. 6/26 downregulated miRNAs reconstituted upon GFD, including miR-150-5p/-3p, whereas no upregula

Celiac disease (CeD) is an immune-mediated disorder triggered by exposure to dietary gluten proteins in genetically predisposed individuals. In addition to the host genome, the microbiome has recently been linked to CeD risk and pathogenesis. To progress in our understanding of the role of breast milk microbiota profiles in CeD, we have analyzed samples from a sub-set of mothers (n = 49) included in the PreventCD project, whose children did or did not develop CeD. The results of the microbiota data analysis indicated that neither the BMI, HLA-DQ genotype, the CeD condition nor the gluten-free diet of the mothers could explain the human milk microbiota profiles. Nevertheless, we found that origin country, the offspring’s birth date and, consequently, the milk sampling date influenced the abundance and prevalence of microbes in human milk, undergoing a transition from an anaerobic to a more aerobic microbiota, including potential pathogenic species. Furthermore, certain microbial species were more abundant in milk samples from mothers whose children went on to develop CeD compared to those that remained healthy. These included increases in facultative methylotrophs such as Methylobacterium komagatae and Methylocapsa palsarum as well as in species such as Bacteroides vulgatus, that consumes fucosylated-oligosaccharides present in human milk, and other breast-abscess associated species. Theoretically, these microbiota components could be vertically transmitted from mothers-to-infants during breastfeeding, thereby influencing CeD risk.

© Copyright © 2020 Benítez-Páez, Olivares, Szajewska, Pieścik-Lech, Polanco, Castillejo, Nuñez, Ribes-Koninckx, Korponay-Szabó, Koletzko, Meijer, Mearin and Sanz. Celiac disease (CeD) is an immune-mediated disorder triggered by exposure to dietary gluten proteins in genetically predisposed individuals. In addition to the host genome, the microbiome has recently been linked to CeD risk and pathogenesis. To progress in our understanding of the role of breast milk microbiota profiles in CeD, we have analyzed samples from a sub-set of mothers (n = 49) included in the PreventCD project, whose children did or did not develop CeD. The results of the microbiota data analysis indicated that neither the BMI, HLA-DQ genotype, the CeD condition nor the gluten-free diet of the mothers could explain the human milk microbiota profiles. Nevertheless, we found that origin country, the offspring’s birth date and, consequently, the milk sampling date influenced the abundance and prevalence of microbes in human milk, undergoing a transition from an anaerobic to a more aerobic microbiota, including potential pathogenic species. Furthermore, certain microbial species were more abundant in milk samples from mothers whose children went on to develop CeD compared to those that remained healthy. These included increases in facultative methylotrophs such as Methylobacterium komagatae and Methylocapsa palsarum as well as in species such as Bacteroides vulgatus, that consumes fucosylated-oligosaccharides present in human milk, and other breast-abscess associated species. Theoretically, these microbiota components could be vertically transmitted from mothers-to-infants during breastfeeding, thereby influencing CeD risk.

© 2018 Hellmuth et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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

Copyright © 2017 ESPGHAN and NASPGHAN. Objectives: Several cases of eating disorders (EDs) have been reported in patients with celiac disease (CD), suggesting that ED could be a comorbidity associated with CD. Few epidemiological studies have, however, assessed this potential association. We aimed to evaluate the risk of EDs in individuals diagnosed with CD in comparison to healthy controls. Methods: A total of 98 cases and 98 controls matched for sex, age, and body mass index between 10 and 23 years old were studied. A questionnaire was completed on medical history and sociodemographic as well as anthropometric characteristics. Various ED screening self-reported tests were administered. Results: A total of 61.2% of the study population were girls with a mean age of 15.3×3.7 years old. Patients with CD scored nonsignificantly higher on all the ED screening tests than control participants. No differences were observed between study groups in terms of the frequency of individuals who exceeded the clinical cutoff identifying those at risk of ED. Patients with CD above 13 years old were associated with a 2.15-point increase in the Eating Attitude Test score compared with controls [b-coefficient=2.15 SE 1.04; P=0.04] after adjusting for various confounders. Conclusions: Although being a patient with CD was associated with a significantly higher Eating Attitude Test score in individuals older than 13 years old, no clear differences were observed between individuals with CD and controls in terms of risk of ED when other screening tests were used. More studies with larger samples and prospective designs are warranted to confirm these findings.

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.

© 2018, © 2018 CSIC. Celiac disease (CD) is an immune-mediated enteropathy involving genetic and environmental factors, whose interaction influences disease risk. The intestinal microbiota, including viruses and bacteria, could play a role in the pathological process leading to gluten intolerance. In this study, we investigated the prevalence of pathogens in the intestinal microbiota of infants at familial risk of developing CD. We included 127 full-term newborns with at least one first-degree relative with CD. Infants were classified according to milk-feeding practice (breastfeeding or formula feeding) and HLA-DQ genotype (low, intermediate or high genetic risk). The prevalence of pathogenic bacteria and viruses was assessed in the faeces of the infants at 7 days, 1 month and 4 months of age. The prevalence of Clostridium perfringens was higher in formula-fed infants than in breast-fed over the study period, and that of C. difficile at 4 months. Among breastfed infants, a higher prevalence of enterotoxigenic E. coli (ETEC) was found in infants with the highest genetic risk compared either to those with a low or intermediate risk. Among formula-fed infants, a higher prevalence of ETEC was also found in infants with a high genetic risk compared to those of intermediate risk. Our results show that specific factors, such as formula feeding and the HLA-DQ2 genotype, previously linked to a higher risk of developing CD, influence the presence of pathogenic bacteria differently in the intestinal microbiota in early life. Further studies are warranted to establish whether these associations are related to CD onset later in life.

© 2017 by the authors. Licensee MDPI, Basel, Switzerland. Gluten-related disorders have recently been reclassified with an emerging scientific literature supporting the concept of non-celiac gluten sensitivity (NCGS). New research has specifically addressed prevalence, immune mechanisms, the recognition of non-immunoglobulin E (non-IgE) wheat allergy and overlap of NCGS with irritable bowel syndrome (IBS)-type symptoms. This review article will provide clinicians with an update that directly impacts on the management of a subgroup of their IBS patients whose symptoms are triggered by wheat ingestion.

© 2017 AGA Institute Background & Aims The guidelines of the European Society of Pediatric Gastroenterology, Hepatology, and Nutrition allow for diagnosis of celiac disease without biopsies in children with symptoms and levels of immunoglobulin A against tissue-transglutaminase (TGA-IgA) 10-fold or more the upper limit of normal (ULN), confirmed by detection of endomysium antibodies (EMA) and positivity for HLA-DQ2/DQ8. We performed a large, international prospective study to validate this approach. Methods We collected data from consecutive pediatric patients (18 years or younger) on a gluten-containing diet who tested positive for TGA-IgA from November 2011 through May 2014, seen at 33 pediatric gastroenterology units in 21 countries. Local centers recorded symptoms; measurements of total IgA, TGA, and EMA; and histopathology findings from duodenal biopsies. Children were considered to have malabsorption if they had chronic diarrhea, weight loss (or insufficient gain), growth failure, or anemia. We directly compared central findings from 16 antibody tests (8 for TGA-IgA, 1 for TGA-IgG, 6 for IgG against deamidated gliadin peptides, and 1 for EMA, from 5 different manufacturers), 2 HLA-DQ2/DQ8 tests from 2 manufacturers, and histopathology findings from the reference pathologist. Final diagnoses were based on local and central results. If all local and central results were concordant for celiac disease, cases were classified as proven celiac disease. Patients with only a low level of TGA-IgA (threefold or less the ULN) but no other results indicating celiac disease were classified as no celiac disease. Central histo-morphometry analyses were performed on all other biopsies and cases were carefully reviewed in a blinded manner. Inconclusive cases were regarded as not ha

OBJECTIVES: To compare the dietary pattern between subjects with coeliac disease (CD) (cases) and subjects without (healthy controls). METHODS: A case-control design study was conducted. A total of 98 subjects with CD (aged 10 to 23 years-old) were matched by age, gender and BMI with 98 non-coeliac participants. A non-consecutive 3-day food record was completed to assess energy, nutrient and food intake and evaluate the participant's adherence to recommendations. Differences in energy, nutrients, food consumption, and compliance with general recommendations between cases and control groups were assessed by Student's t-test. Pearson's chi-squared test was used to compare categorical variables. Socio-demographic, personal and family history data were collected. RESULTS: Compared to the control group, the CD cases reported a significantly higher consumption of added sugar (P < 0.001) and total fat (P < 0.017). Mean fiber consumption was below nutritional recommendations in both groups. CD participants consumed significantly lower amounts of foods rich in starch (P < 0.001), and higher amounts of foods rich in protein such as meat/fish/eggs (P = 0.007). CD subjects showed a significantly lower percentage of adherence to recommendations for folic acid (53.2 vs 70.5; P < 0.001), calcium (49.0 vs 56.3; P = 0.025), iron (57.4 vs 78.0; P < 0.001) and magnesium (50.0 vs 63.9; P < 0.001). CONCLUSION: The CD subjects showed a more unbalanced diet than controls in terms of added sugars, total fat and micronutrient consumption.

OBJECTIVES: The aim of the study was to compare the dietary pattern between subjects with celiac disease (CD) (cases) and subjects without (healthy controls) CD. METHODS: A case-control design study was conducted. A total of 98 subjects with CD (age 10-23 years) were matched by age, sex, and body mass index with 98 nonceliac participants. A nonconsecutive 3-day food record was completed to assess energy, nutrient, and food intake and evaluate the participant's adherence to recommendations. Differences in energy, nutrients, food consumption, and compliance with general recommendations between cases and control groups were assessed by Student t test. Pearson chi-squared test was used to compare categorical variables. Sociodemographic, personal, and family history data were collected. RESULTS: Compared with the control group, the cases with CD reported a significantly higher consumption of added sugar (P < 0.001) and total fat (P < 0.017). Mean fiber consumption was below the nutritional recommendations in both groups. Participants with CD consumed significantly lower amounts of foods rich in starch (P < 0.001) and higher amounts of foods rich in protein such as meat, fish, and eggs (P = 0.007). Subjects with CD showed a significantly lower percentage of adherence to recommendations for folic acid (53.2 vs 70.5; P < 0.001), calcium (49.0 vs 56.3; P = 0.025), iron (57.4 vs 78.0; P < 0.001), and magnesium (50.0 vs 63.9; P < 0.001). CONCLUSIONS: The subjects with CD showed a more unbalanced diet than controls in terms of added sugars, total fat, and micronutrient consumption.

Objectives: Treatment for celiac disease (CD) is a lifelong strict gluten-free diet (GFD). Patients should be followed-up with dietary interviews and serology as CD markers to ensure adherence to the diet. However, none of these methods offer an accurate measure of dietary compliance. Our aim was to evaluate the measurement of gluten immunogenic peptides (GIP) in stools as a marker of GFD adherence in CD patients and compare it with traditional methods of GFD monitoring. Methods: We performed a prospective, nonrandomized, multicenter study including 188 CD patients on GFD and 84 healthy controls. Subjects were given a dietary questionnaire and fecal GIP quantified by enzyme-linked immunosorbent assay (ELISA). Serological anti-tissue transglutaminase (anti-tTG) IgA and anti-deamidated gliadin peptide (anti-DGP) IgA antibodies were measured simultaneously.Results: Of the 188 celiac patients, 56 (29.8%) had detectable GIP levels in stools. There was significant association between age and GIP in stools that revealed increasing dietary transgressions with advancing age (39.2% in subjects ≥13 years old) and with gender in certain age groups (60% in men ≥13 years old). No association was found between fecal GIP and dietary questionnaire or anti-tTG antibodies. However, association was detected between GIP and anti-DGP antibodies, although 46 of the 53 GIP stool-positive patients were negative for anti-DGP.Conclusions: Detection of gluten peptides in stools reveals limitations of traditional methods for monitoring GFD in celiac patients. The GIP ELISA enables direct and quantitative assessment of gluten exposure early after ingestion and could aid in the diagnosis and clinical management of nonresponsive CD and refractory CD. Trial registration number NCT02711397.

© 2016 Elsevier Ltd Objectives and study In the development of Celiac Disease (CD) both genetic and environmental factors play a crucial role. The Human Leukocyte Antigen (HLA)-DQ2 and HLA-DQ8 loci are strongly related to the disease and are necessary but not sufficient for the development of CD. Therefore, increasing interest lies in examining the mechanisms of CD onset from the early beginning. Differences in serum and urine metabolic profiles between healthy individuals and CD patients have been reported previously. We aimed to investigate if the metabolic pathways were already altered in young, 4 month old infants, preceding the CD diagnosis. Methods Serum samples were available for 230 four month old infants of the PreventCD project, a multicenter, randomized, double-blind, dietary intervention study. All children were positive for HLA-DQ2 and/or HLA-DQ8 and had at least one first-degree relative diagnosed with CD. Amino acids were quantified after derivatization with liquid chromatography – tandem mass spectrometry (MS/MS) and polar lipid concentrations (acylcarnitines, lysophosphatidylcholines, phosphatidylcholines, and sphingomyelins) were determined with direct infusion MS/MS. We investigated the association of the metabolic profile with (1) the development of CD up to the age of 8 years (yes/no), (2) with HLA-risk groups, (3) with the age at CD diagnosis, using linear mixed models and cox proportional hazards models. Gender, intervention group, and age at blood withdrawal were included as potential confounder. Results By the end of 2014, thirty-three out of the 230 children (14%) were diagnosed with CD according to the ESPGHAN criteria. Median age at diagnosis was 3.4 years (IQR, 2.4–5.2). Testing each metabolite for a difference in the mean between healthy an

The European Society for Paediatric Gastroenterology, Hepatology and Nutrition recommended in 2008, based on observational data, to avoid both early (<4 months) and late (?7 months) introduction of gluten and to introduce gluten while the infant is still being breast-fed. New evidence prompted ESPGHAN to revise these recommendations.To provide updated recommendations regarding gluten introduction in infants and the risk of developing coeliac disease (CD) during childhood.The risk of inducing CD through a gluten-containing diet exclusively applies to persons carrying at least one of the CD risk alleles. Because genetic risk alleles are generally not known in an infant at the time of solid food introduction, the following recommendations apply to all infants, although they are derived from studying families with first-degree relatives with CD. Although breast-feeding should be promoted for its other well-established health benefits, neither any breast-feeding nor breast-feeding during gluten introduction has been shown to reduce the risk of CD. Gluten may be introduced into the infant's diet anytime between 4 and 12 completed months of age. In children at high risk for CD, earlier introduction of gluten (4 vs 6 months or 6 vs 12 months) is associated with earlier development of CD autoimmunity (defined as positive serology) and CD, but the cumulative incidence of each in later childhood is similar. Based on observational data pointing to the association between the amount of gluten intake and risk of CD, consumption of large quantities of gluten should be avoided during the first weeks after gluten introduction and during infancy. The optimal amounts of gluten to be introduced at weaning, however, have not been established.

© 2015 by the authors; licensee MDPI, Basel, Switzerland. Non-Celiac Gluten Sensitivity (NCGS) is a syndrome characterized by intestinal and extra-intestinal symptoms related to the ingestion of gluten-containing food, in subjects that are not affected by either celiac disease or wheat allergy. Given the lack of a NCGS biomarker, there is the need for standardizing the procedure leading to the diagnosis confirmation. In this paper we report experts’ recommendations on how the diagnostic protocol should be performed for the confirmation of NCGS. A full diagnostic procedure should assess the clinical response to the gluten-free diet (GFD) and measure the effect of a gluten challenge after a period of treatment with the GFD. The clinical evaluation is performed using a self-administered instrument incorporating a modified version of the Gastrointestinal Symptom Rating Scale. The patient identifies one to three main symptoms that are quantitatively assessed using a Numerical Rating Scale with a score ranging from 1 to 10. The double-blind placebo-controlled gluten challenge (8 g/day) includes a one-week challenge followed by a one-week washout of strict GFD and by the crossover to the second one-week challenge. The vehicle should contain cooked, homogeneously distributed gluten. At least a variation of 30% of one to three main symptoms between the gluten and the placebo challenge should be detected to discriminate a positive from a negative result. The guidelines provided in this paper will help the clinician to reach a firm and positive diagnosis of NCGS and facilitate the comparisons of different studies, if adopted internationally.

BACKGROUND A window of opportunity has been suggested for reducing the risk of celiac disease by introducing gluten to infants at 4 to 6 months of age. METHODS We performed a multicenter, randomized, double-blind, placebo-controlled dietary-intervention study involving 944 children who were positive for HLA-DQ2 or HLA-DQ8 and had at least one first-degree relative with celiac disease. From 16 to 24 weeks of age, 475 participants received 100 mg of immunologically active gluten daily, and 469 received placebo. Anti-transglutaminase type 2 and antigliadin antibodies were periodically measured. The primary outcome was the frequency of biopsy-confirmed celiac disease at 3 years of age. RESULTS Celiac disease was confirmed by means of biopsies in 77 children. To avoid underestimation of the frequency of celiac disease, 3 additional children who received a diagnosis of celiac disease according to the 2012 European Society for Pediatric Gastroenterology, Hepatology, and Nutrition diagnostic criteria (without having undergone biopsies) were included in the analyses (80 children; median age, 2.8 years; 59% were girls). The cumulative incidence of celiac disease among patients 3 years of age was 5.2% (95% confidence interval [CI], 3.6 to 6.8), with similar rates in the gluten group and the placebo group (5.9% [95% CI, 3.7 to 8.1] and 4.5% [95% CI, 2.5 to 6.5], respectively; hazard ratio in the gluten group, 1.23; 95% CI, 0.79 to 1.91). Rates of elevated levels of anti-transglutaminase type 2 and antigliadin antibodies were also similar in the two study groups (7.0% [95% CI, 4.7 to 9.4] in the gluten group and 5.7% [95% CI, 3.5 to 7.9] in the placebo group; hazard ratio, 1.14; 95% CI, 0.76 to 1.73). Breast-feeding, regardless of whether it was exclusive or whether it was ongoing during gluten introduction, did not significantly influence the development of celiac disease or the effect of the intervention. CONCLUSIONS As compared with placebo, the introduction of small quantiti