No one is born with celiac disease, yet some individuals are predisposed to its development, based on two main factors. The transition from gluten tolerance to onset occurs in a subset of individuals who both carry the human leukocyte antigen (HLA)-DQ2 or HLA-DQ8 alleles in their genetic makeup (30%-40%) and consume gluten. What transpires to foment evolution in approximately 3% of these individuals, and why it happens, is of interest to benefit public health. At issue is the tipping point, where deamidated gluten peptides acquire increased affinity and binding to specific HLA-DQ2/DQ8 molecules on the surface of antigen-presenting cells (APCs), thereby alerting CD4+ T-cells to inflict damage on small intestinal mucosa. Is the transition to celiac disease caused by an alteration in the special manner that gluten peptides, deamidated by transglutaminase, are bound, and how strongly they are bound on the APCs, to render them recognizable as antigen by CD4+ T-cells? Or does the transformation occur when the CD4+ T-cells are rendered immunogenic to the tightly bound and deamidated gluten peptides on the APCs? Are supplementary conditions crucial? Might the modification be reversible under certain circumstances? It is suggested that onset may be triggered by the cumulative burden of extrinsic inflammatory factors vs anti-inflammatory factors acting on a genetically susceptible host consuming gluten, rather than arising from a sole insult. A paradigm to possibly reduce the odds of developing the disease, and to reduce the time needed for recovery after diagnosis, is presented. Implications for incorporating modern gastrointestinal endoscopic techniques are discussed.

BACKGROUND:Proton pump inhibitors (PPIs) are widely used for upper gastrointestinal symptoms but are frequently prescribed inappropriately and often continued without clear indications. Deprescribing PPIs can be challenging due to symptom recurrence or rebound acid hypersecretion. The mucosal protective agent Poliprotect, a natural formulation with barrier, antioxidant, and anti-inflammatory properties, has shown non-inferiority to omeprazole in non-erosive heartburn and epigastric pain syndrome (EPS) without affecting intestinal microbiota. AIM:To evaluate the role of Poliprotect formulation (neoBianacid) in maintaining symptom control after PPI withdrawal in patients with endoscopy-negative heartburn (HRTB) and EPS. METHODS:This post hoc analysis used data from a multicenter, double-blind RCT including 125 endoscopy-negative patients (80 with HRTB, 45 with EPS) treated with omeprazole 20 mg/day for 4 weeks, followed by 4 weeks of on-demand Poliprotect after PPI discontinuation. Outcomes included symptom severity (VAS), responder rate (≥ 50% VAS reduction), use of rescue medication, quality of life (GIQLI), gastrointestinal symptoms (GSRS), treatment satisfaction, and safety. RESULTS:At the end of deprescription, mean VAS scores remained stable, and 69.5% of PPI responders (65.8%, HRTB, and 76.2%, EPS) maintained symptom control. Additionally, 31% of PPI non-responders (33.3%, HRTB, and 27.3%, EPS) became responders with Poliprotect. Rescue antacid use and quality of life scores were not significantly changed. No adverse events were reported during the deprescribing phase. CONCLUSIONS:On-demand Poliprotect was associated with maintenance of symptom control after PPI withdrawal and outcome improvement in approximately one-third of PPI non-responders. Poliprotect appears to be a safe, well-tolerated, and promising strategy to support PPI discontinuation in endoscopy-negative heartburn and EPS patients. TRIAL REGISTRATION:Clinicaltrial.gov (NCT03238534) and EudraCT Database (2015-005216-15).

BACKGROUND:Primary intestinal B-cell (IBCL) and T-cell (ITCL) lymphomas are rare and poorly characterized entities. AIM:To compare clinical features and survival outcomes of IBCL and ITCL. METHODS:We conducted a multicentre, retrospective study including patients diagnosed with primary intestinal lymphoma between 2001 and 2024. Clinical and laboratory variables were analysed using univariate and multivariate logistic regression. Discriminatory accuracy was assessed through ROC analysis. Overall survival was estimated with Kaplan-Meier curves. RESULTS:Ninety-four patients (41 IBCL and 53 ITCL) were included. IBCL were more frequently diagnosed at Lugano stage I (90% vs 5.7%; p<0.01) and showed markedly lower lactate dehydrogenase and β2-microglobulin levels compared with ITCL (p<0.01). Coeliac disease (CD) was strongly associated with ITCL (p<0.01). In multivariable analysis, CD and biomarker levels independently differentiated IBCL from ITCL, with excellent model discrimination (AUROC 0.95). Median follow-up was 56 months for IBCL and 12 months for ITCL. IBCL demonstrated significantly greater survival (HR 0.21; log-rank p=0.01). CONCLUSIONS:IBCL and ITCL exhibit distinct clinical and prognostic profiles, with IBCL showing more favourable clinical profile and better survival. Tailored diagnostic and therapeutic approaches that reflect the divergent behaviour of these lymphomas are urgently needed.

Evidence suggests that a gluten-free diet may increase the risk of metabolic abnormalities associated with cardiovascular disease in adults with Coeliac Disease (CeD). This 9-week, double-blind, placebo-controlled, randomised pilot study investigated the effects of a combined supplement containing probiotic Lactiplantibacillus plantarum ECGC 13110402 and plant sterols and stanols, on cardiometabolic biomarkers and gut microbiota diversity and composition in adults with CeD and hypercholesterolaemia. Blood lipid profiles and vitamin D concentrations were analysed, and gut microbiota was profiled via 16S rRNA amplicon sequencing. In the active group, significant reductions in total cholesterol, LDL-cholesterol, non-HDL cholesterol, and apolipoprotein B were observed at multiple time points during the treatment phase, with changes generally greater in magnitude compared with the placebo group. Vitamin D levels also increased in the active group during supplementation. Microbiota analysis revealed potentially beneficial changes in participants receiving the active formulation, including higher alpha diversity and higher proportions of Bifidobacterium spp., Christensenellaceae R-7 group, and Lachnospiraceae ND3007 group. Overall, this feasibility study provides exploratory findings that a combined Lactiplantibacillus plantarum ECGC 13110402-phytosterol formulation may support lipid management and beneficially modulate gut microbiota in adults with CeD, particularly for those seeking non-pharmacological approaches to improving cardiometabolic health biomarkers.

Despite more women entering medicine, women in gastroenterology continue to experience disparities in training, research and career opportunities. United European Gastroenterology calls to ensure that everyone has equal access to opportunities, mentoring and supportive workplaces that will benefit both professionals and patients.

Non-coeliac gluten sensitivity (NCGS) refers to individuals who report intestinal and extraintestinal symptoms related to the ingestion of gluten-based or wheat-based foods, in the absence of coeliac disease or wheat allergy. Gluten is found in multiple cereals, including wheat, rye, and barley, although the precise trigger of symptoms in NCGS remains unclear. Although approximately 10% of adults worldwide self-report gluten or wheat sensitivity, meta-analyses suggest that, during controlled challenge studies, 16-30% of these individuals have symptoms specifically triggered by gluten. However, methodological variability-including the presence of fermentable carbohydrates in challenge preparations-limits interpretation. Current evidence suggests that fermentable carbohydrates and nocebo effects contribute considerably to symptom generation in many cases. The substantial size of the gluten-free market raises questions about commercial and media influences on how NCGS is portrayed, and on the direction of related research. Definitive diagnosis of NCGS remains elusive due to the absence of biomarkers, significant overlap with disorders of gut-brain interaction, and methodological challenges in dietary evaluation. Until causative agents are identified and diagnostic tests developed, NCGS remains a diagnosis of exclusion, requiring careful systematic evaluation. Management approaches should balance dietary modification with recognition of psychological factors while ensuring nutritional adequacy. This Review critically examines current evidence regarding NCGS as a distinct entity, explores potential mechanisms, and provides practical guidance for assessment and management, while acknowledging major uncertainties in the field.

Artificial Intelligence's (AI) role in providing information on Celiac Disease (CD) remains understudied. This study aimed to evaluate the accuracy and reliability of ChatGPT-3.5 in generating responses to 20 basic CD-related queries. This study assessed ChatGPT-3.5, the dominant publicly accessible version during the study period, to establish a benchmark for AI-assisted CD education. The accuracy of ChatGPT's responses to twenty frequently asked questions (FAQs) was assessed by two independent experts using a Likert scale, followed by categorization based on CD management domains. Inter-rater reliability (agreement between experts) was determined through cross-tabulation, Cohen's kappa, and Wilcoxon signed-rank tests. Intra-rater reliability (agreement within the same expert) was evaluated using the Friedman test with post hoc comparisons. ChatGPT demonstrated high accuracy in responding to CD FAQs, with expert ratings predominantly ranging from 4 to 5. While overall performance was strong, responses to management strategies excelled compared to those related to disease etiology. Inter-rater reliability analysis revealed moderate agreement between the two experts in evaluating ChatGPT's responses (κ = 0.22, p-value = 0.026). Although both experts consistently assigned high scores across different CD management categories, subtle discrepancies emerged in specific instances. Intra-rater reliability analysis indicated high consistency in scoring for one expert (Friedman test=0.113), while the other exhibited some variability (Friedman test<0.001). ChatGPT exhibits potential as a reliable source of information for CD patients, particularly in the domain of disease management.

Celiac disease (CeD) is an autoimmune disorder, causing significant gastrointestinal (GI) and non-GI symptoms. The only effective treatment is a gluten-free diet (GFD), but adherence can be challenging. This study investigates GFD adherence among CeD patients and the change in their clinical and pathological conditions over time. A telephone-based retrospective observational analysis conducted between November 2022 and June 2023 enrolled 300 participants with confirmed CeD, selected via systematic sampling from an initial cohort of 1,268 individuals. A comprehensive questionnaire assessed demographics, clinical symptoms, and GFD adherence. Participants were categorized into short/meidum-term (≤ 6 months), long-term (6–24 months), and very long-term (≥ 24 months) GFD adherence groups. All statistical analyses were conducted using R (version 4.3.1), employing a variety of packages tailored for descriptive and inferential statistics. Participants’ mean age was 41.58 (± 12.37) years, with females constituting 73.67

Celiac disease (CeD) diagnosis traditionally relies on detecting serum antibodies against gluten, transglutaminase 2, and anti-endomysial antibodies, as well as confirming mucosal damage via intestinal biopsy. While serology is useful in diagnosing CeD, guidelines for adults often recommend an upper endoscopy and duodenal biopsy to assess mucosal atrophy. Human leukocyte antigens (HLA) testing is also valuable; Histology remains essential in presence of low-titer serology. In the presence of serology positive at high titers, in children and adults CeD cases can be diagnosed without biopsy. A gluten challenge may be necessary for accurate diagnosis in individuals already on a gluten-free diet. Research is in progress to develop less invasive diagnostic methods.

This review highlights gender gaps in training, career, and work-life balance in gastroenterology. Stereotypes and biases toward women's abilities and commitment to their careers can influence evaluations, advancement in gastroenterology training, and career progression. The findings indicate that lack of or limited access to mentorship and sponsorship, as well as support networks, can hinder the professional development of women. Moreover, results indicate that we must improve work-life balance measures, for example offering flexible working hours and compensation and support for women during pregnancy, after childbirth, and motherhood. However, reports on such equity measures are scarce, and we lack scientific evidence of their impact. This review concludes that to reduce gender gaps and make a positive impact, we need educational and promotional programs and monitoring of their outcomes.

Introduction Gastroenterology training usually coincides with childbearing years and pregnancy and parenthood during training can impact trainees’ work–life–family balance. Aim The aim was to assess the challenges that gastroenterology trainees in Europe encounter during pregnancy and parenthood. Methodology A questionnaire was distributed electronically, targeting doctors who were pregnant or had a pregnant partner during their gastroenterology training in the last 10 years. Results The study included 82 women and 22 nonpregnant partners. Fear of being perceived negatively was prevalent ( n = 59, 72.0%) as well as concern that the pregnancy would negatively impact on training ( n = 54, 65.9%). Participants reported several hazards that were not addressed during pregnancy, namely exposure to non-scavenged anesthetic gases (34.1%) and exposure to blood-borne illnesses (28.0%). Formal training programs’ maternity leave policies were reported by only 34.1% ( n = 28) of women and 45.5% ( n = 10) of men. Satisfaction with the duration of parental leave was 85.1% ( n = 63) for women and 50% ( n = 11) for men. Women reported greater difficulty coping with early parenthood during gastroenterology training than men (women: n = 14, 18.4% vs. men: n = 10, 45.5%; P = 0.014) while worrying that having children would impair their career progress (women: n = 40, 52.6% vs. men: n = 8, 36.4%; P = 0.015). Conclusion This European study has demonstrated perceptions of negative stigma related to childbearing, concerns of unaddressed health hazards, dissatisfaction with parental leave policies and a desire for more discussion on a healthy work–family–life balance.

Background/Objectives: Large language models (LLMs) show promise for patient education, yet their safety and efficacy for chronic diseases requiring lifelong management remain unclear. This study presents the first comprehensive comparative evaluation of three leading LLMs for celiac disease patient education. Methods: We conducted a cross-sectional evaluation comparing ChatGPT-4, Claude 3.7, and Gemini 2.0 using six blinded clinical specialists (four gastroenterologists and two dietitians). Twenty questions spanning four domains (general understanding, symptoms/diagnosis, diet/nutrition, lifestyle management) were evaluated for scientific accuracy, clarity (5-point Likert scales), misinformation presence, and readability using validated computational metrics (Flesch Reading Ease, Flesch-Kincaid Grade Level, SMOG index). Results: Gemini 2.0 demonstrated superior performance across multiple dimensions. Gemini 2.0 achieved the highest scientific accuracy ratings (median 4.5 [IQR: 4.5-5.0] vs. 4.0 [IQR: 4.0-4.5] for both competitors, p = 0.015) and clarity scores (median 5.0 [IQR: 4.5-5.0] vs. 4.0 [IQR: 4.0-4.5], p = 0.011). While Gemini 2.0 showed numerically lower misinformation rates (13.3% vs. 23.3% for ChatGPT-4 and 24.2% for Claude 3.7), differences were not statistically significant (p = 0.778). Gemini 2.0 achieved significantly superior readability, requiring approximately 2-3 fewer years of education for comprehension (median Flesch-Kincaid Grade Level 9.8 [IQR: 8.8-10.3] vs. 12.5 for both competitors, p < 0.001). However, all models exceeded recommended 6th-8th grade health literacy targets. Conclusions: While Gemini 2.0 demonstrated statistically significant advantages in accuracy, clarity, and readability, misinformation rates of 13.3-24.2% across all models represent concerning risk levels for direct patient applications. AI offers valuable educational support but requires healthcare provider supervision until misinformation rates improve.

INTRODUCTION:Small bowel adenocarcinoma (SBA) and T-cell lymphoma (TCL) are rare but aggressive malignancies associated with celiac disease (CD). METHODS:We retrospectively compared 43 CD-associated SBA and 43 CD-associated TCL across international referral centers. RESULTS:CD-associated SBA showed a significantly ( P < 0.01) better survival than CD-associated TCL. TCL more frequently presented with multifocal involvement and advanced stage, whereas SBA predominantly involved the jejunum. Refractoriness to a gluten-free diet was identified in 70% of TCL but only in one SBA. DISCUSSION:Our findings demonstrated a worse prognosis of CD-associated TCL in comparison with CD-associated SBA.

Purpose of review Celiac disease (CeD) is a chronic autoimmune disorder of the small intestine triggered by gluten ingestion in genetically predisposed individuals. The cornerstone of CeD management remains a strict adherence to a lifelong gluten-free diet (GFD), although such a dietary restriction can lead to an altered quality of life and may not be easy to follow for many patients. These challenges highlighted the need for alternative therapies. This review aims to explore the latest advancements in these therapeutic avenues, emphasizing mechanisms of action, clinical efficacy, and safety profiles of drugs currently in advanced stages of clinical testing. Recent findings Recent advances in the understanding of CeD pathophysiology have catalyzed the development of new therapeutic approaches, which include strategies to modify gluten processing in the gut, block gluten-triggered immune responses, or restore immune tolerance to gluten. Summary While these therapies are not poised to take the place of GFD, they represent promising treatment alternatives that could enhance the quality of life and minimize long-term consequences in CeD patients. Further research, as well as phase III clinical trials of those already conducted, are needed to establish the feasibility of integrating these novel drugs in the clinical management of CeD.

Celiac disease (CeD) is a chronic immune-mediated disorder of the small intestine triggered by the ingestion of dietary gluten. This narrative review aims to summarize and critically evaluate the recent literature on the association between CeD and infertility, with an emphasis on identifying patterns and inconsistencies. Previous studies have reported conflicting findings: while some demonstrate a higher prevalence of unexplained infertility in patients with CeD, others do not support this association. Overall, untreated CeD may be a contributing factor to infertility, especially unexplained cases, and a gluten-free diet (GFD) might improve fertility outcomes. However, the general prevalence of infertility in CeD patients does not appear to exceed that of the general population. This review includes evidence on both male and female infertility and examines possible pathophysiological mechanisms, including nutritional deficiencies, immune-mediated effects, and sexual dysfunction. Further high-quality prospective studies are needed to determine the true impact of CeD on reproductive health and to inform screening guidelines.

Background Increased levels of pro-inflammatory proteins in plasma can be detected in older individuals and associate with the so called chronic low-grade inflammation, which contributes to a faster progression of aged-related cardiovascular (CV) diseases, including frailty, neurodegeneration, gastro-intestinal diseases and disorders reflected by alterations in the composition of gut microbiota. However, successful genetic programme of long-living individuals alters the trajectory of the ageing process, by promoting an efficient immune response that can counterbalance deleterious effects of inflammation and the CV complications. This is the case of BPIFB4 gene in which, homozygosity for a four single-nucleotide polymorphism (SNP) haplotype, the Longevity-Associated Variant (LAV) correlates with prolonged health span and reduced risk of CV complications and inflammation. The relation between LAV-BPIFB4 and inflammation has been proven in different experimental models, here we hypothesized that also human homozygous carriers of LAV-BPIFB4 gene may experience a lower inflammatory burden as detected by plasma proteomics that could explain their favourable CV risk trajectory over time. Moreover, we explored the therapeutic effects of LAV-BPIFB4 in inflammatory disease and monolayer model of intestinal barrier. Results We used high-throughput proteomic approach to explore the profiles of circulating proteins from 591 baseline participants selected from the PLIC cohort according to the BPIFB4 genotype to identify the signatures and differences of BPIFB4 genotypes useful for health and disease management. The observational analysis identified a panel of differentially expressed circulating proteins between the homozygous LAV-BPIFB4 carriers and the other alternative BPIFB4 genotypes highlighting in the latter ones a higher grade of immune-inflammatory markers. Moreover, in vitro studies performed on intestinal epithelial organs from inflammatory bowel disease (IBD) patients and monolayer model of intestinal barrier demonstrated the benefit of LAV-BPIFB4 treatment. Conclusions Homozygosity for LAV-BPIFB4 results in the attenuation of inflammation in PLIC cohort and IBD patients providing preliminary evidences for its therapeutic use in inflammatory disorders that need to be further characterized and confirmed by independent studies.