The presence of human leukocyte antigen (HLA)-DQ2 and/or HLA-DQ8 alleles is necessary but not sufficient for the development of celiac disease (CeD). This suggests that additional environmental and biological factors, including bacteria and, above all, the still rarely studied fungal gut microbiota, play key roles in disease onset and progression. To characterize and compare the intestinal bacteriobiota and mycobiota profiles of children with newly diagnosed CeD and their unaffected siblings, in comparison with a healthy control group. The study included children and adolescents aged 1 to 18 years. Participants were divided into three groups: (1) 14 patients with newly diagnosed CeD; (2) 16 asymptomatic siblings of CeD patients; and (3) 19 healthy children (control group). Stool samples were collected from all eligible participants. Next-generation sequencing was performed, followed by analysis of the relationship between the gut microbiota and genetic predisposition to CeD, with attention to the HLA DQ2/8 alleles. Regarding alpha diversity, the CeD and sibling groups differed significantly from the control group (bacteria), and the CeD group differed from siblings (fungi). Significant dissimilarities in beta diversity were observed between siblings and both CeD and control groups. In comparisons between CeD group and their siblings, 13 indicator bacterial species were identified, whereas in comparisons between the CeD group and their siblings and controls, 8 indicator fungal species were detected. No significant correlation was found between bacterial species and the presence of the HLA DQ2.5 allele, or between fungal species and HLA DQ2.2. A strong (r = 0.8-0.9) positive relationship was found between Subdoligranulum variabile and several bacterial species. A moderate (r = 0.4-0.7) positive correlation was observed between the fungal species Microidium phyllanthi and Bifidobacterium longum, Clostridium leptum and Romboutsia timonensis. While DQ2.5 plays a central role in disease pathogenesis, it appears to have less direct influence on microbial composition. The distinct fungal signatures observed in siblings may serve as early indicators of risk and warrant further investigation.

To determine the human leukocyte antigen (HLA)-DQ genotype pattern in children with celiac disease (CD). We retrospectively reviewed 490 patients aged 2-18years who presented to our clinic between 2014 and 2024 with suspected CD and underwent HLA-DQ tissue typing. Out of 490 patients, 220 were diagnosed as CD and 270 as controls. Analysis of CD samples for HLA types revealed that 140 (63.6%) were only HLA-DQ2 positive, 25 (11.3%) were only HLA-DQ8 positive, and 35 (15.9%) were both HLA-DQ2 and HLA-DQ8 positive. However, 20 (9%) of our patients were neither HLA-DQ2 nor HLA-DQ8 positive. In the control group, 102 patients were HLA-DQ2 positive and 66 were HLA-DQ8 positive Being homozygous for HLA-DQ2 increased the risk for CD by 16.49 times, and being homozygous for HLA-DQ8 increased the risk for CD by 4.39 times. HLA-DQ2/8 genotypes are strongly associated with pediatric patients with CD in Turkey. These genotypes and their combinations do not alter clinical presentation. HLA-DQ2/8 strongly contributes to the development of CD.

This study demonstrates overall compliance with ESPGHAN guidelines, although gaps persist in biopsy orientation and follow-up timing for patients with persistent TGA-IgA positivity. The use of novel endoscopic technologies is still limited, indicating the need for further studies and dedicated training programs to support their implementation in clinical practice. • Diagnostic pitfalls in celiac disease remain a major challenge in endoscopy practice. • New endoscopic tools proved to be useful to decrease the number of misdiagnoses and related healthcare costs of celiac disease. • Major gaps remain regarding proper orientation of biopsies, and the timing of follow-up endoscopy in patients with persistent TGA-IgA positivity. • Further studies and dedicated training programs are required to facilitate the effective integration of advanced endoscopic technologies into the diagnostic workflow.

There is a strikingly disproportionate female-to-male ratio in diagnoses of autoimmune, neurological, and chronic pain disorders. Although biological mechanisms—such as hormonal fluctuations, X-linked genetic factors, immune modulation, and epigenetic vulnerability—are frequently proposed, no single pathway sufficiently accounts for the magnitude of this imbalance. Across diagnostic categories, these conditions share a constellation of symptoms: persistent fatigue, cognitive slowing or “brain fog,” diffuse musculoskeletal pain, gastrointestinal disturbance, autonomic irregularities, numbness, breathlessness, and dizziness. Notably, this symptom profile echoes early twentieth-century descriptions of hysteria, a diagnosis historically applied to women whose distress manifested through bodily complaints. This article does not argue for diagnostic equivalence, but rather for conceptual continuity. It considers whether contemporary conditions such as Fibromyalgia, Celiac disease, Ehlers-Danlos syndrome, Premenstrual dysphoric disorder, and Long COVID might, in some cases, represent embodied expressions of unarticulated strain within sociocultural systems that have historically constrained female agency. Drawing on theoretical frameworks and clinical vignettes, the paper explores how trauma, chronic stress physiology, immune dysregulation, and gendered role expectations intersect. It ultimately advocates for an integrative model—medical, psychodynamic, and somatic—that treats women’s symptoms as meaningful communications shaped by both biology and lived experience, rather than as evidence of defect or fragility. This perspective seeks to shift the narrative from women's bodies as "broken" to bodies expressing deeper truths that Western medicine has yet to fully understand.

BackgroundObservational studies have reported associations between autoimmune diseases (AIDs) and colorectal cancer (CRC), but whether these relationships are causal remains unclear.MethodsWe performed a bidirectional two-sample Mendelian randomization (MR) analysis to evaluate the causal effects of eight prevalent AIDs—systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), ankylosing spondylitis (AS), gout, multiple sclerosis (MS), celiac disease (CD), eczema, and asthma—on CRC risk, and to examine the possibility of reverse causation. Genome-wide association study (GWAS) summary statistics from individuals of European ancestry were analyzed. The inverse-variance weighted (IVW) approach served as the primary MR estimator, with MR-Egger regression and the weighted median method applied as complementary analyses. Robustness was further evaluated through sensitivity analyses, including assessments of heterogeneity and horizontal pleiotropy.ResultsGenetically predicted CD was associated with a reduced risk of CRC (IVW odds ratio (OR) = 0.94; 95% confidence interval (CI), 0.89–0.99; P = 0.028). Genetically predicted RA was associated with an increased risk of CRC (IVW OR = 1.06; 95% CI, 1.02–1.11; P = 0.004). No significant causal associations were observed for the other AIDs. Reverse MR provided no evidence that genetic liability to CRC causally influenced the risk of these AIDs. Sensitivity analyses supported the stability of the findings.ConclusionsThis bidirectional MR study provides genetic evidence supporting unidirectional, modest causal effects of specific AIDs (CD and RA) on CRC risk. Further studies are warranted to clarify underlying mechanisms, including immune dysregulation, inflammation, and dietary factors, and to determine clinical implications.

Background: The oral cavity is sometimes referred to as a “diagnostic window” of systemic health, as even subtle systemic disturbances can manifest as changes in the oral mucosa. Coeliac disease, diabetes mellitus, and inflammatory bowel diseases (IBD) are chronic conditions that frequently present with oral mucosal lesions, which may precede or accompany the classical symptoms of these diseases. Aim: To systematically review and compare the oral mucosal changes reported in coeliac disease, diabetes mellitus, and IBD. The most common clinical manifestations are characterized, potential pathophysiological mechanisms are discussed, and the relevance of oral findings for early recognition and monitoring of these systemic diseases is evaluated. Materials and Methods: A systematic literature search was conducted in PubMed and Google Scholar using combinations of English keywords (including “oral mucosa,” “oral manifestations,” “coeliac disease,” “diabetes mellitus,” “inflammatory bowel disease,” “Crohn’s disease,” “ulcerative colitis,” “aphthous ulcers,” “xerostomia,” “oral microbiome,” and “oral–gut axis”). A total of 37 relevant peer-reviewed articles (clinical studies and reviews) were identified and analyzed. Results: The most frequently described oral manifestations in these conditions include recurrent aphthous stomatitis, inflammatory and atrophic changes of the tongue (such as geographic tongue and atrophic glossitis), angular cheilitis, xerostomia, and recurrent opportunistic infections (especially oral candidosis). In coeliac disease, oral lesions (aphthae, glossitis, cheilitis) and dental enamel defects often occur, sometimes even years before diagnosis, and tend to improve after the introduction of a strict gluten-free diet. Diabetes is associated with salivary gland dysfunction leading to dry mouth, elevated salivary glucose, and immune dysfunction – factors that contribute to candidosis, poor wound healing, burning mouth sensations, and an increased incidence of oral ulcers. IBD (Crohn’s disease and ulcerative colitis) can produce a broad spectrum of oral changes: Crohn’s disease in particular is characterized by specific granulomatous lesions (such as persistent lip swelling, mucosal “cobblestoning,” and deep linear ulcers) as well as nonspecific lesions (recurrent aphthae, pyostomatitis vegetans, glossitis, cheilitis). Oral manifestations of IBD are more common in Crohn’s disease and in pediatric patients and can precede intestinal symptoms or correlate with intestinal disease activity. Conclusions: Oral mucosal changes represent an important extraintestinal component of coeliac disease, diabetes, and IBD. They can serve as early warning signs of these disorders or indicators of disease activity and control. Recognition of characteristic oral lesions by dentists and physicians is crucial, as it can expedite diagnosis and prompt timely management (e.g. initiation of a gluten-free diet in coeliac disease or improved glycemic control in diabetes). Regular oral examinations should be an integral part of the care of patients with these conditions. Interdisciplinary collaboration – especially between dentists, gastroenterologists, and diabetologists – is essential for early detection, comprehensive monitoring, and improved patient outcomes.

Immune-related enteropathies (IREs) represent a heterogeneous group of disorders characterised by immune-mediated small bowel injury. While coeliac disease is the most common cause, widespread use of small bowel endoscopy has expanded the recognition of rarer causes. This review aims to summarise recent advances in diagnosis, classification and management of IRE. Significant overlap exists between coeliac disease, autoimmune enteropathy, collagenous sprue, drug-induced enteropathies, common variable immunodeficiency (CVID) associated enteropathy and other IRE. A recent meta-analysis supports a no-biopsy approach in selected adults with significantly elevated IgA tissue transglutaminase levels and suspected coeliac disease. Refractory coeliac disease type II is now recognised as a low-grade intraepithelial T-cell lymphoma with a high risk of progression to enteropathy-associated T-cell lymphoma (EATL). Drug-induced enteropathies, particularly olmesartan-associated enteropathy, are increasingly detected and may mimic autoimmune enteropathy histologically. Novel therapeutic approaches, including cladribine, JAK inhibitors and biologics, have shown promise in refractory disease, although evidence is limited to small studies. IREs present substantial diagnostic and therapeutic challenges due to overlapping characteristics and variable disease course. A structured approach integrating clinical, serological and histopathological data is essential for accurate diagnosis. Early recognition and tailored management are crucial to prevent long-term complications.

BackgroundZinc deficiency (ZD) is one of the most prevalent nutritional deficiencies reported in celiac disease (CeD). Oral supplementation and dietary modifications are the primary strategies for addressing it. However, it is unclear whether individuals with CeD would prefer to make additional dietary modifications or opt for supplementation to treat ZD.AimThis study aimed to explore patient preferences for the treatment of ZD.MethodsAdult patients (≥18 years) with a confirmed diagnosis of CeD who were already adopting a gluten-free diet (GFD) and had untreated ZD were recruited from the Adult Celiac Disease Clinic at McMaster University. After providing informed consent, participants completed study questionnaires at baseline and three months after initiating zinc supplementation. Data were collected using REDCap. Statistical analyses were performed using IBM SPSS software (V22, Chicago, USA).ResultsFrom March 2022 to January 2024, 44 participants were enrolled in the study. All completed baseline questionnaires, of them 25 (57%) completed questionnaires at follow-up. At baseline, 34% of participants preferred to treat nutrient deficiencies through dietary changes, compared with 28% at follow-up. Plasma zinc level normalized in all participants after 3 months of supplementation. At follow-up, the proportion of participants with significant gastrointestinal symptoms increased from 72% at baseline to 80% (p = 0.01).ConclusionsOne-third of patients with CeD preferred to manage nutrient deficiencies through dietary modifications. A zinc-optimized GFD may represent a promising approach to address zinc deficiency in this population. These findings provide preliminary evidence to inform the design of future randomized clinical trials.

The gastrointestinal tract harbours a vast chemical diversity of small molecules, consisting of dietary nutrients, microorganism-derived metabolites and metabolic products of the host. The latest evidence highlights a direct involvement of different metabolites in the diverse aetiologies of intestinal diseases, ranging from inflammatory to metabolic and neoplastic conditions. The accessibility of the gastrointestinal tract to oral intervention suggests that fine-tuning the levels of intestinal metabolites might be a promising and currently underutilized therapeutic strategy. Here, we provide a conceptual overview of the recurring mechanistic themes by which metabolites shape the biology of immune cells, epithelium and neurons of the gastrointestinal tract. Additionally, we classify metabolites according to possible categories of therapeutic intervention, and summarize the latest preclinical and clinical data unveiling the roles of intestinal metabolites in the pathophysiology of major diseases of the gastrointestinal tract, including inflammatory bowel disease, irritable bowel syndrome, colorectal cancer, enteric infection, food allergy, coeliac disease, as well as obesity and metabolic syndrome. In each case, we provide an overview of the mechanisms by which intestinal metabolites have been associated with disease aetiology. In addition, we discuss possible metabolite-based strategies for intervention. Our overall goal is to provide a roadmap towards developing metabotherapies for intestinal disease.

Celiac Disease: Conventional and Novel Biomarkers.

Dissecting the genetic relationship between severe mental disorders and autoimmune diseases.

Enhancing gluten modification for celiac patients: harnessing microbial transglutaminase, ε-poly-l-lysine, and prolyl endopeptidase.

Rethinking coeliac disease care: why psychological understanding matters

Background Neurological and psychiatric morbidity has been associated with celiac disease but has been scarcely studied in dermatitis herpetiformis (DH), a cutaneous manifestation of celiac disease. Hence, this cohort study aimed to investigate neurological and psychiatric morbidity in patients with DH and celiac disease. Methods The study comprised 368 DH patients and 1,072 celiac disease patients without DH and their 1,099 and 3,197 refences, matched 1:3 on age, sex, calendar period and place of residence. Their neurological and psychiatric morbidity was studied using the Care Register for Health Care and international classification of diseases codes. Hazard ratios (HR) were calculated using Cox proportional hazard model. Results In DH the risk for any neurological disease was not statistically significantly increased (HR 1.27; 95% CI 0.94–1.71), but Alzheimer’s disease and extrapyramidal diseases were found to be more common in DH when compared with their references. In contrast, in celiac disease excess risks for any neurological disease (HR 1.31; 95% CI 1.09–1.56) and particularly for migraine and headaches were detected. The risk for any psychiatric disease was found to be decreased in DH (HR 0.65; 95% CI 0.47–0.90), as were the risks for anxiety and substance abuse. In celiac disease, increased risks for any psychiatric disease (HR 1.20; 95% CI 1.01–1.42), depression, and anxiety disorders were noted. Conclusions The neurological and psychiatric morbidity of patients with DH and celiac disease patients without DH seems to differ, but the reasons for this varying disease burden remain yet unidentified.

Background and Clinical Significance: Celiac disease (CD) is a gluten-triggered immune enteropathy that may rarely present as Celiac crisis (CC), a life-threatening condition marked by severe diarrhea, dehydration, metabolic derangements, and acute malnutrition. Pediatric diagnostic criteria are lacking, and despite its reduced incidence in high-income countries, CC remains a critical complication, potentially associated with refeeding syndrome. Case Presentation: We report the case of a 23-month-old girl presenting with chronic diarrhea, weight loss, iron-deficiency anemia, hypoalbuminemia, and coagulation abnormalities. Serology confirmed CD, and a gluten-free diet (GFD) was initiated. However, the patient experienced clinical deterioration consistent with CC. Her course was further complicated by refeeding syndrome, ileo-ileal intussusception, and deep vein thrombosis, requiring corticosteroids, anticoagulation, and multidisciplinary nutritional support. Full clinical recovery was achieved within two months. Conclusions: This case highlights the life-threatening potential of CC and the necessity for early recognition. Timely GFD initiation, correction of metabolic abnormalities, and monitoring for refeeding syndrome are essential. We propose pediatric-adapted diagnostic criteria to facilitate earlier recognition and standardize the management of CC. The proposed framework includes major and minor criteria based on the rapid onset of gastrointestinal symptoms with serological evidence of CD autoimmunity, accompanied by clinical instability requiring hospitalization or intensive support and multiple indicators of systemic compromise.

Objective The anti-endomysial antibody (EMA) immunofluorescence test is recommended by some clinical guidelines as an adjunct to immunoglobulin A anti-tissue transglutaminase (TTG) antibody in coeliac disease (CD) diagnosis. However, dual testing can complicate interpretation. We assessed the diagnostic value of EMA alongside TTG. Method We retrospectively analysed patients tested for TTG and EMA between 2018 and 2019 at a single laboratory. 587 patients were categorised into two groups: TTG 7–10 U/mL (‘borderline’) and TTG >10 U/mL. CD was confirmed by duodenal biopsy; if unavailable, TTG ≥100 U/mL (10×upper limit of normal) was diagnostic, serologically. Results Biopsies were performed in all borderline cases (n=41). Among 23 EMA-negative patients, 17 (74%) had biopsy-confirmed CD. 12 of 18 (67%) EMA-positive patients had CD. EMA showed poor sensitivity (0.4138) and specificity (0.5000). Fisher’s exact test found no association between EMA and biopsy results (p=0.7341), indicating EMA’s limited diagnostic value in borderline cases. In the TTG >10 U/mL group (n=546), 523 were EMA-positive (511 with CD, 98%). Of 23 EMA-negative patients, 14 (61%) had CD. Despite a statistically significant association with CD (p<0.0001), EMA added minimal clinical value (sensitivity 0.9733; specificity 0.4286). Conclusion EMA had low sensitivity in borderline cases and added no diagnostic value when TTG was positive. We recommend discontinuing EMA testing in clinical practice. The high rate of CD in borderline cases suggests that current TTG diagnostic thresholds need reconsideration. Prospective, multicentre replication using standardised assays is required to evaluate whether biopsies are warranted at lower TTG values than currently recommended.

Immune reconstitution in pediatric HIV infection under antiretroviral therapy (ART) is monitored by CD4 + T-cell counts and the CD4/CD8 ratio, whereas the role of double-negative T cells (DNTs; CD3 + CD4 - CD8 - ) is poorly defined. We aimed to characterize CD4 + /CD8 + T-cell dynamics and age-dependent DNT patterns. In this retrospective cohort, 30 children were followed for 12 months after ART initiation. Flow cytometry was used to measure CD3 + , CD4 + , CD8 + and DNT subsets and the CD4/CD8 ratio; demographic, clinical and coinfection data were abstracted from medical records. The cohort comprised 30 children (20 boys, 10 girls; mean age 10.4 years). ART increased CD4 + and decreased CD8 + T-cell percentages, with the CD4/CD8 ratio rising from 0.73 to 1.09 and normalizing (≥1.0) in 63.3% of children. Baseline DNT levels were elevated (mean 7.0%) but declined significantly, normalizing (<5%) in adolescents, whereas children 0-5 years maintained higher residual levels. Higher DNT percentages correlated with lower CD4 + counts and an inverted CD4/CD8 ratio. Cytomegalovirus and Epstein-Barr virus viremia were common; in 3 children with dual cytomegalovirus/Epstein-Barr virus viremia, baseline CD4 + percentages were lower and DNT percentages higher, and 1 had celiac disease, suggesting that dual viremia on a background of immune-mediated disease may delay immune reconstitution. DNT% reduction showed a trend toward greater decrease with integrase inhibitor-based regimens. In pediatric HIV infection, CD4/CD8 ratio normalization and DNT decline depict a more nuanced immune reconstitution than CD4 + recovery alone. Age-dependent DNT trajectories support incorporating DNT monitoring as a complementary biomarker in pediatric ART management.

Exploring the Immunological Shield Hypothesis: A Population-Based Exploration of Phenotypic Divergence Between Lipedema and Celiac Disease Autoimmunity

ABSTRACT Gastrointestinal (GI) diseases remain among the leading causes of global mortality, with early detection directly linked to survival outcomes. While previous reviews have focused on single imaging modalities, this systematic review uniquely examines artificial intelligence applications across endoscopic, radiological, and histological approaches, reflecting actual clinical diagnostic pathways. This systematic review analyzes 76 high‐quality studies (2016–2024) and provides the first comprehensive assessment of how AI performs across different imaging techniques for GI abnormality detection. This multi‐modal perspective is particularly timely as healthcare systems move toward integrated diagnostic workflows. Our analysis reveals endoscopy as the most widely used modality ( n = 44), particularly for Helicobacter pylori , colorectal polyps, and ulcerative colitis detection. Histological analysis emerges as the second most common approach ( n = 25), especially for celiac disease and ulcerative colitis, while CT imaging ( n = 10) primarily supports colorectal polyp detection. Deep learning methods significantly outnumber traditional machine learning techniques (68 vs. 8 studies), consistently achieving 90%–99% diagnostic accuracy across multiple disease categories. However, these systems face significant implementation barriers to clinical adoption. Most validation is still conducted in controlled, single‐center settings using curated datasets that poorly reflect clinical complexity. Future studies must prioritize multicenter validation, standardized imaging protocols and preprocessing pipelines, and the integration of interpretable AI models capable of providing transparent diagnostic rationale. This review maps the current technical landscape while highlighting critical translational challenges that must be addressed to enable real‐world impact. This article is categorized under: Technologies &gt; Data Preprocessing Technologies &gt; Artificial Intelligence

Diagnostic Accuracy of Biopsy-Sparing Approaches in Adult Celiac Disease.