Background In pediatric patients, celiac disease (CD) may influence the health-related quality of life (HRQoL). Aims The study aimed to assess HRQoL and further characterise the clinical factors associated with reduced HRQoL, in a large multicenter pediatric cohort with CD. Methods The disease-specific questionnaire CD Dutch Questionnaire (CDDUX) and the generic questionnaire Paediatric Quality of Life Inventory (PedsQL) were used to assess the HRQoL. Clinical and sociodemographic characteristics were analyzed, univariate and multivariate analysis were conducted. Results Eleven different Italian pediatric centers and 871 families were involved. Mean age at interview was 12.9 ± 2.9 years. The mean total CDDUX score of CD patients was 47.1 ± 18.8, revealing a neutral HRQoL (47.1 ± 18.8), and a good to very good HRQoL according to the PedsQL (81.4 ± 12.6), parents indicated lower scores (p = 0.03) with both questionnaires (CDDUX 45.1 ± 18.6 and PedsQL 79.9 ± 14.5). Patients with lower HRQoL were mainly female, living in Northern Italy, with lower parent's education level and non-biopsy diagnosis of CD. In multivariate analysis, the main predictor of lower CDDUX score was non-biopsy diagnosis. Conclusions The HRQoL in a large cohort of Italian children is reported as neutral-good. This indicates a high level of adaptive behaviors in response to the daily challenges of CD. Parents tend to underestimate their children's HRQoL. Specific clinical factors, including non-biopsy diagnosis, may be associated to lower HRQoL.

Background/Objectives. Rules for gluten-free (GF) food varies throughout the world. A maximum gluten level of 20 parts per million (ppm) in GF items is allowed in countries adopting the Codex Alimentarius recommendation, e.g. USA, Canada, UK, and the EU. More stringent criteria (no detectable gluten) are requested in other countries, e.g. Australia. However, only few data are available on the toxicity/safety of gluten traces in the diet of patients with celiac disease (CeD). The aim of this review was to review the scientific background of the gluten threshold in GF food. Methods. Studies on the dose-effect relationship between the amount of low gluten and detectable damage in CeD patients were examined and critically reviewed within the context of the current Codex Alimentarius rules. Results. A gluten dose higher than 10 mg per day, corresponding to 500 g of daily GF products at 20 ppm, may be harmful for most CeD patients. There is wide inter-patient variability in the response to a gluten intake of 10 mg. The potential toxicity of gluten traces < 10 mg/day of gluten remains unclear. Conclusions. The 20 ppm gluten threshold is safe for most patients, however further randomized controlled trials are required to evaluate the effects of 0-10 mg/day of gluten intake and, consequently, the safety of the current threshold at 20 ppm for “hypersensitive” CeD patients. New techniques, e.g. IL-2 measurement after a single-dose gluten challenge, may facilitate the investigation of the gluten dose-response curve, particularly in the low range of gluten intake.

Abstract Background Mesalamine (5-ASA) is recommended as a first-line medication for inducing and maintaining remission in mild to moderate ulcerative colitis (UC), but indications regarding its use in children with moderate to severe disease treated with biologics are lacking. We aimed to evaluate whether discontinuing 5-ASA might impact the outcomes of children with UC treated with anti-TNFα. Methods Retrospective, single-center, case-control study of children with UC receiving anti-TNFα therapy between January 2018 and January 2023 and with a minimum follow of 6 months. Children who discontinued 5-ASA within six months from the biological therapy initiation were compared to those who continued mesalamine as maintenance therapy. Every 6 months, during a 2-year follow-up, major outcomes defined as disease flares, IBD-related hospitalization, surgery, need for step-up treatment were recorded. Results Ninety-eight children were included in the final analysis, 51 (52%) maintained 5-ASA and 47 (48%) discontinued 5-ASA. The 2 groups were comparable for all the baseline clinical and demographic characteristics. At 6 months, the cumulative incidence of major outcomes, acute severe colitis and need for step up treatment was significantly higher in children who discontinued 5-ASA (p < 0.05). Throughout the follow-up period, children who discontinued 5-ASA were at significant higher risk of hospitalization (Log Rank p=0.02), need for step up treatment (Log Rank p=0.02) and acute severe colitis (Log Rank p=0.003). Conclusion Our data suggest that 5-ASA discontinuation might have a negative impact on the clinical course of children with UC treated with anti-TNFα in terms of major outcomes. However, conclusive evidence regarding this matter requires prospective randomized trials.

BACKGROUND:Whether primary sclerosing cholangitis related to inflammatory bowel disease (PSC-IBD) diagnosed before 6 years (ie, VEO-IBD) has a distinct phenotype and disease course is uninvestigated. We aimed to analyze the characteristics and natural history of VEO-PSC-IBD, compared with early and adolescent-onset PSC-IBD. METHODS:This is a multicenter, retrospective, case-control study from 15 centers affiliated with the Porto and Interest IBD group of ESPGHAN. Demographic, clinical, laboratory, endoscopic, and imaging data were collected at baseline and every 6 months. Inflammatory bowel disease-related (clinical remission, need for systemic steroids and biologics, and surgery) and PSC-related (biliary and portal hypertensive complications, need for treatment escalation and liver transplantation, cholangiocarcinoma, or death) outcomes were compared between the 2 groups. RESULTS:Sixty-nine children were included, with a median follow-up of 3.63 years (interquartile range, 1-11): 28 with VEO-PSC-IBD (23 UC [82%], 2 IBD-U [7%] and 3 [11%] CD), and 41 with PSC-IBD (37 UC [90%], 3 IBDU [7.5%] and 1 [2.5%] CD). Most patients with UC presented with pancolitis (92% in VEO-PSC-UC vs 85% in PSC-UC, P = .2). A higher number of patients with VEO-PSC-IBD were diagnosed with PSC/autoimmune hepatitis overlap syndrome than older children (24 [92%] vs 27 [67.5%] PSC-IBD, P = .03), whereas no other differences were found for PSC-related variables. Time to biliary strictures and infective cholangitis was lower in the VEO-PSC-IBD group (P = .01 and P = .04, respectively), while no difference was found for other outcomes. No cases of cholangiocarcinoma were reported. CONCLUSIONS:Primary sclerosing cholangitis related to inflammatory bowel disease has similar baseline characteristics whether diagnosed as VEO-IBD or thereafter. A milder disease course in terms of biliary complications characterizes VEO-PSC-IBD.

A new chemiluminescence immunoassay method (CLIA) for detecting IgA anti-transglutaminase (atTG IgA) in celiac disease (CD) has prompted inquiries into its diagnostic performance. We conducted a systematic review and meta-analysis comparing CLIA with traditional enzyme-linked immunosorbent assay (ELISA) and fluorescence enzyme immunoassay (FEIA). We searched PubMed, Medline, and Embase databases up to March 2024. The diagnostic references were intestinal biopsy and ESPGHAN guidelines. We calculated the sensitivity and specificity of atTG IgA assessed by CLIA and the odds ratio (OR) between the assays. Eleven articles were eligible for the systematic review and seven for the meta-analysis. Sensitivity and specificity of atTG IgA CLIA-assay were 0.98 (95% CI, 0.95–0.99) and 0.97 (95% CI, 0.94–0.99), respectively. The sensitivity of atTG IgA antibody detection did not significantly vary across the three assay modalities examined (CLIA vs. ELISA OR: 1.08 (95% CI, 0.56–2.11; p = 0.8); CLIA vs. FEIA OR: 6.97 (95% CI, 0.60–81.03; p = 0.1). The specificity of atTG IgA assessed by FEIA was higher than for CLIA (OR 0.17 (95% CI, 0.05–0.62); p < 0.007). According to the systematic review, normalization of atTG IgA levels in CD patients following a gluten-free diet was delayed when using CLIA compared to ELISA and FEIA methods. Conflicting findings were reported on the antibody threshold to use in order to avoid biopsy confirmation.

OBJECTIVES: This study described disease characteristics and long-term outcomes in patients diagnosed with very early onset inflammatory bowel disease (VEOIBD) (diagnosed before 6 years of age) and infantile-IBD (before 2 years). METHODS: Cases from 21 centers worldwide diagnosed with VEOIBD (2008-2018), with minimum 2 years of follow-up, were retrospectively reviewed. RESULTS: The cohort included 243 patients (52% males, median follow-up of 5.8 [range 2-18] years, including 69 [28%]) with infantile-IBD. IBD subtypes included Crohn's disease (CD), ulcerative colitis (UC), or IBD-unclassified (IBDU) in 30%, 59%, and 11%, respectively. Among patients with CD, 94% had colonic involvement, and among patients with UC/IBDU, 75% had pancolitis. Patients with infantile-IBD presented with higher rates of IBDU, lower hemoglobin and albumin levels, and higher C-reactive protein, and had lower response rates to first-induction therapy and corticosteroids therapy (P < .05 for all). Colectomy and diversion surgeries were performed in 11% and 4%, respectively, with no significant differences between age groups. Corticosteroid-free remission rates were 74% and 78% after 3 and 5 years, respectively, and 86% at end of follow-up. Genetic testing was performed in 96 (40%) patients. Among tested population, 15 (16%) were identified with monogenic disease. This group demonstrated lower response rates to induction therapies, higher rates of surgical intervention, and higher rates of major infections (P < .05 for all). CONCLUSIONS: Patients with VEOIBD, including infantile-IBD, exhibit low rate of complications and surgical interventions at the long term. Patients with monogenic IBD are at risk for more severe disease course.

Crohn’s Disease (CD) is a chronic inflammatory disorder of the gastrointestinal tract, posing diagnostic and management challenges due to its potential involvement of any segment from the mouth to the anus. Device-assisted enteroscopy (DAE) has emerged as a significant advancement in the management of CD, particularly for its ability to access the small intestine—a region difficult to evaluate with conventional endoscopic methods. This review discusses the pivotal role of DAE in the nuanced management of CD, emphasizing its enhanced diagnostic precision and therapeutic efficacy. DAE techniques, including double-balloon enteroscopy (DBE), single-balloon enteroscopy (SBE), and the now-withdrawn spiral enteroscopy, enable comprehensive mucosal assessment, targeted biopsies, and therapeutic interventions like stricture dilation, bleeding control, and foreign body removal. Despite its benefits, DAE carries risks such as perforation, bleeding, and pancreatitis, which require careful procedural planning and a skilled execution. The review highlights DAE’s impact on reducing surgical interventions and improving patient outcomes through minimally invasive approaches, thereby enhancing the quality of life for patients with CD. Continuous improvement and research are essential in order to maximize DAE’s utility and safety in clinical practice.

OBJECTIVES:Patients with inflammatory bowel disease (IBD) tend to self-modify their dietary habits according to disease activity and symptoms. This study aimed to assess the adequacy of the usual diet in Italian children with IBD in comparison to a control group and to the recommended dietary allowances (RDA). METHODS:Dietary habits of IBD children and age- and gender-matched healthy controls were investigated using a validated Food Frequency Questionnaire in five Italian pediatric IBD centers. Adherence to the Mediterranean diet (MD) was assessed using the KID-MED test. Energy (EI), macro, and micronutrients intakes were compared between the two groups, to the RDA and the predicted total energy expenditure (EI/total energy expenditure [TEE]%). RESULTS:IBD subjects (n = 110) reported a lower EI, EI/RDA%, and EI/TEE% compared to controls (n = 110) (p = 0.012, p < 0.0002, and p = 0.014), lower total protein and fat intakes (p = 0.017, p < 0.0001) and lower minerals/RDA, vitamins/RDA and micronutrients/RDA ratio (%). Poor adherence to the MD was more frequent in IBD children compared to controls (p = 0.013). The total EI and carbohydrate intake were inversely correlated with higher disease activity. CONCLUSIONS:Italian children with IBD report an inadequate diet in terms of energy, macro, and micronutrients and have a low adherence to a high-quality MD pattern.

This narrative review describes the settlement of the neonatal microbiome during the perinatal period and its importance on human health in the long term. Delivery methods, maternal diet, antibiotic exposure, feeding practices, and early infant contact significantly shape microbial colonization, influencing the infant’s immune system, metabolism, and neurodevelopment. By summarizing two decades of research, this review highlights the microbiome’s role in disease predisposition and explores interventions like maternal vaginal seeding and probiotic and prebiotic supplementation that may influence microbiome development. Conclusion: The perinatal period is a pivotal phase for the formation and growth of the neonatal microbiome, profoundly impacting long-term health outcomes.

Abstract Background The multicentre OXIBDiet trial (NCT04513015) has already demonstrated a redox imbalance in IBD children compared to adults and controls. The second part of the study aimed to evaluate the impact of an Antioxidant Diet (AoD) in comparison to a Mediterranean Diet (MD) in IBD patients. Clinical outcomes and nutritional data are reported. Methods IBD children and adults with mild symptoms/remission were randomly assigned to AoD (polyphenols intake >650 mg/die) or MD for 12 weeks. In the paediatric sample a Free Diet (FD) group was enrolled. At baseline and at 12 weeks inflammatory, oxidative stress (OS), clinical and anthropometric parameters were recorded. Dietary habits were registered by a validated Food Frequency Questionnaire and nutritional intakes were estimated with Winfood software. Results Twenty-five children (10 OD, 10 MD, 5 FD) and 17 adults (9 OD, 8 MD) completed the study. The total antioxidant capacity (Ferric reducing antioxidant power, FRAP) of the total IBD cohort significantly increased only in AoD (p=0.024) group and the Protein Oxidation (AOPP) showed a trend of decrease in AoD group (p=0.065). Stratifying for age, the same results of FRAP emerged only in the paediatric sample, following the AoD (Figure 1). Weight z-score (p=0.04) and BMI z-score (p=0.054) increased significantly in children following the AoD. The AoD groups both in children and in adults showed respectively a significant improved in health status (p=0.016) and in Food Related QoL. Faecal calprotectin (FC) showed a trend toward reduction both in AoD and MD groups and an increase in the FD group. At week 0 dietetic habits and nutrients intakes were similar in children in the AoD and MD groups. Changes in nutrients intakes at week 12 for both groups are reported in Table 1. In AoD group of IBD children a significant positive correlation between FRAP and intake of polyphenols emerged (p=0.015). Conclusion Preliminary results showed a significant improvement in OS imbalance and anthropometric parameters in IBD subject following an AoD. Antioxidant micronutrients intakes increased in IBD children especially on AoD, with a positive effect on the total antioxidant capacity. Also, QoL and Faecal calprotectin showed a favourable trend in AoD group, both in children and in adults. Final results of the study will allow to clarify the role of oxidative stress and antioxidants in IBD pathogenesis and treatment.

Gluten-related disorders (GRD) include celiac disease (CD), non celiac gluten sensitivity (NCGS) and wheat allergy (WA), conditions that are associated with the ingestion of gluten-containing food. Gut microbiota composition and function may be involved in the pathogenesis of GRD. In untreated CD the microbiota is characterized by a reduction in beneficial microbes like Lactobacillus and Bifidobacterium and an increase in pathogenic ones such as Bacteroides and E. coli. Dysbiosis is a hallmark of CD, persists across various disease stages and is only partially corrected by a gluten-free diet. NCGS patients show a different microbial profile, with a notable decrease in microbial richness, and an increase of Ruminococcaceae and decrease of Bacteroidetes and Fusobacteria. The increase of certain bacterial groups such as Clostridium and Anaerobacter, in contrast with the decline of Bacteroides and Clostridium XVIII, marks a distinctive microbial signature associated with allergic responses to food. Mechanisms linking the gut microbiota to the development of GRD include effects on the gut barrier function, microbiota-mediated immune response to gluten, and an impact of microbial metabolites on gluten digestion and tolerance.Although the gluten-free diet is the primary therapy of GRDs, treatment with probiotics may contribute to improve the natural history of these disorders, for instance by minimizing the damaging effects of gluten contamination and accelerating the catch-up growth at the beginning of the dietary treatment of CD. Additional high-quality trials are still needed to identify and standardize the use of probiotics/prebiotics in GRDs.

BackgroundFacebook (FB) is the most popular online networking platform. Many celiac disease Facebook (CD-FB) pages spread awareness about celiac disease (CD). To get the latest information, patients with CD frequently follow such pages. However, little is known about whether such pages provide authentic and reliable information.AimsThis study aims to investigate whether CD-FB pages spread misleading information to patients with CD.MethodsOn the Facebook social networking platform, CD-FB pages created in three celiac-prevalent countries (Italy, the USA, and India) were explored using different combinations of keywords. The type/category of the CD-FB page, country of origin, purpose, page web link, and number of followers/members were documented in a Microsoft spreadsheet. All posts distributed on selected CD-FB pages in the last 3 years were thoroughly screened.ResultsFrom August 2022 to March 2023, a total of 200 CD-FB pages from Italy, the USA, and India were explored. Out of these 200 pages, 155 CD-FB (Italy 70; the USA 46; India 39) were found eligible. Of them, 20 (13%) CD-FB pages (Italy 4; the USA 5; India 11) shared misleading information about CD. Surprisingly, 11 (8%) of these 20 pages (Italy 0; the USA 2; India 9) supported alternative treatment options for CD.ConclusionsCD-FB pages are useful for disseminating celiac-disease-related information. While most such pages provide useful information, 13% of CD-FB pages allow misleading information. Patients with CD should consult their treating unit before following any uncertain information posted on CD-FB pages.

The infant gut microbiome plays a key role in the healthy development of the human organism and appears to be influenced by dietary practices through multiple pathways. First, maternal diet during pregnancy and infant nutrition significantly influence the infant gut microbiota. Moreover, breastfeeding fosters the proliferation of beneficial bacteria, while formula feeding increases microbial diversity. The timing of introducing solid foods also influences gut microbiota composition. In preterm infants the gut microbiota development is influenced by multiple factors, including the time since birth and the intake of breast milk, and interventions such as probiotics and prebiotics supplementation show promising results in reducing morbidity and mortality in this population. These findings underscore the need for future research to understand the long-term health impacts of these interventions and for further strategies to enrich the gut microbiome of formula-fed and preterm infants.

Objective Food products with <20 mg/kg gluten can be labeled ‘gluten-free’ according to international regulations. Several antibodies-based ELISAs have been develop to track gluten traces in food products. Among them, R5 and G12 antibody-based ELISAs are the frequently used methods. However, these antibodies have certain limitations. We evaluated the accuracy of G12/A1 antibody-based ‘Glutentox ELISA Rapid G12’ and compared the results with the current reference method i.e., R5 antibody-based ‘Ridascreen R5 ELISA’. Methods In the first step, the performance of Glutentox ELISA Rapid G12 kit was inspected by determination of the threshold value i.e., > or <20 mg/kg gluten in different food products. In the second step, quantification accuracy was assessed by quantification of gluten in gluten-free food products spiked with gliadin reference material. Results In total 47 food products (naturally and labeled gluten-free, and food with traces of gluten) were included. Of them, 29 products were quantified with <20 mg/kg, and 18 with a low level of gluten by both the kits. Six out of 29 gluten-free products were used for the recovery test at different spike levels. Gluten concentration and mean recovery rates of individual kits showed consistency. Conclusion GlutenTox Rapid G12 ELISA could be an appropriate choice for detecting gluten in food products but needs more in-house validation and collaborative tests.