Celiac disease (CD), a gluten-related disease, is a multi-system rare disorder mainly involving the gastrointestinal tract. The clinical signs of CD are exceedingly heterogeneous, which increases the difficulty of clinical differential diagnosis. Neurological manifestations are one of the non-classical CD symptoms. As some patients present only neurological symptoms at early stages, the diagnosis of CD is always delayed. Correct diagnosis and management could decrease patient morbidity and deaths. A 32-year-old male was admitted to the hospital due to progressive muscle atrophy of both lower limbs and lumbar stiffness. Based on positive gluten-sensitive enteropathy autoantibody profiles and gastroscopy foundation, the diagnosis of CD was established. The patient was instructed to gluten-free diet. The antibody titer of gluten-sensitive enteropathy autoantibodies decreased, and the patient\'s symptoms alleviated. We emphasize the importance of CD screening in patients with neurological disorders of unknown aetiology.

Microbial transglutaminase (mTG) is a frequently consumed processed food additive, and use of its cross-linked complexes is expanding rapidly. It was designated as a processing aid and was granted the generally recognized as safe (GRAS) classification decades ago, thus avoiding thorough assessment according to current criteria of toxicity and public health safety. In contrast to the manufacturer\'s declarations and claims, mTG and/or its transamidated complexes are proinflammatory, immunogenic, allergenic, pathogenic, and potentially toxic, hence raising concerns for public health. Being a member of the transglutaminase family and functionally imitating the tissue transglutaminase, mTG was recently identified as a potential inducer of celiac disease. Microbial transglutaminase and its docked complexes have numerous detrimental effects. Those harmful aspects are denied by the manufacturers, who claim the enzyme is deactivated when heated or by gastric acidity, and that its covalently linked isopeptide bonds are safe. The present narrative review describes the potential side effects of mTG, highlighting its thermostability and activity over a broad pH range, thus, challenging the manufacturers\' and distributers\' safety claims. The national food regulatory authorities and the scientific community are urged to reevaluate mTG\'s GRAS status, prioritizing public health protection against the possible risks associated with this enzyme and its health-damaging consequences.

Mammalian transglutaminases, a family of Ca2+-dependent proteins, are implicated in a variety of diseases. For example, celiac disease (CeD) is an autoimmune disorder whose pathogenesis requires transglutaminase 2 (TG2) to deamidate select glutamine residues in diet-derived gluten peptides. Deamidation involves the formation of transient γ-glutamyl thioester intermediates. Recent studies have revealed that in addition to the deamidated gluten peptides themselves, their corresponding thioester intermediates are also pathogenically relevant. A mechanistic understanding of this relevance is hindered by the absence of any structure of Ca2+-bound TG2. We report the X-ray crystallographic structure of human TG2 bound to an inhibitory gluten peptidomimetic and two Ca2+ ions in sites previously designated as S1 and S3. Together with additional structure-guided experiments, this structure provides a mechanistic explanation for how S1 regulates formation of an inhibitory disulfide bond in TG2, while also establishing that S3 is essential for γ-glutamyl thioester formation. Furthermore, our crystallographic findings and associated analyses have revealed that i) two interacting residues, H305 and E363, play a critical role in resolving the thioester intermediate into an isopeptide bond (transamidation) but not in thioester hydrolysis (deamidation); and ii) residues N333 and K176 stabilize preferred TG2 substrates and inhibitors via hydrogen bonding to nonreactive backbone atoms. Overall, the intermediate-state conformer of TG2 reported here represents a superior model to previously characterized conformers for both transition states of the TG2-catalyzed reaction.

METHODS: Celiac disease (CD) is an allergic intestinal disease caused mainly by gliadin in wheat, which is widespread in the population and currently lacks effective treatment. α-Gliadin peptides cause cellular damage by substantially increasing cellular reactive oxygen species (ROS) levels.
RESULTS: This study investigates the protective effect of 11 pea-derived peptides (PPs) on ɑ-gliadin peptide (P31-43) treated Caco-2 cells. Results show that cells treated with PP2, PP5, and PP6 peptides significantly reduce the cell mortality caused by P31-43. Three PPs significantly reduce the P31-43-induced decrease in ROS levels to control levels, and there is no difference between them and the vitamin C (Vc) group. The results in terms of antioxidant-related enzymes show that PPs significantly decrease superoxide dismutase activity (SOD), glutathione reductases (GR), and glutathione (GSH)/oxidized glutathione (GSSG) levels, thus significantly enhancing the antioxidant level of cells. By studying the key proteins of the Kelch-like ECH-associated protein 1 (Keap1)/NF-E2-related factor 2 (Nrf2) pathway, it is found that PPs activate the Keap1/Nrf2 signaling pathway.
CONCLUSIONS: The study finds that peptides from peas can effectively alleviate ɑ-gliadin peptide-induced cell damage. The discovery of these food-derived peptides provides novel potential solutions for the prevention and treatment of CD.

Celiac Disease (CD) is a primary malabsorption syndrome resulting from the interplay of genetic, immune, and dietary factors. CD negatively impacts daily activities and may lead to conditions such as osteoporosis, malignancies in the small intestine, ulcerative jejunitis, and enteritis, ultimately causing severe malnutrition. Therefore, an effective and rapid differentiation between healthy individuals and those with celiac disease is crucial for early diagnosis and treatment. This study utilizes Raman spectroscopy combined with deep learning models to achieve a non-invasive, rapid, and accurate diagnostic method for celiac disease and healthy controls. A total of 59 plasma samples, comprising 29 celiac disease cases and 30 healthy controls, were collected for experimental purposes. Convolutional Neural Network (CNN), Multi-Scale Convolutional Neural Network (MCNN), Residual Network (ResNet), and Deep Residual Shrinkage Network (DRSN) classification models were employed. The accuracy rates for these models were found to be 86.67%, 90.76%, 86.67% and 95.00%, respectively. Comparative validation results revealed that the DRSN model exhibited the best performance, with an AUC value and accuracy of 97.60% and 95%, respectively. This confirms the superiority of Raman spectroscopy combined with deep learning in the diagnosis of celiac disease.

BACKGROUND: Celiac disease (CD) is defined as an autoimmune disease (AD) caused by gluten ingestion in genetically sensitive individuals. Several publications have demonstrated the increased risk of AD in patients with CD, both adults and children, which requires systematic research. Our study aimed to determine the prevalence of AD in 60 patients diagnosed with CD and to highlight risk factors that may contribute to the emergence of AD.
METHODS: We collected medical data from all CD patients under 16 years of age who also had AD. Our study was conducted in the Gastroenterology-Hepatology and Pediatric Nutrition Unit of the Pediatrics Department of the Mohamed VI Hospital and University Center in Oujda, Morocco, during a seven-year period between January 2017 and January 2024.
RESULTS: We studied 60 patients with CD in our study. Eight patients (13%) had an associated AD. Their average age was eight years, with extremes varying between two and 15 years. AD was diagnosed before CD in six cases (75%), in parallel with CD in one patient (12.5%), while in only one case, it was diagnosed after CD (12.5%). All our patients had a single AD associated with CD. These ADs were mainly type 1 diabetes in seven cases and autoimmune thyroiditis in only one case. All our patients followed a gluten-free diet in addition to specific treatment for associated AD. Nevertheless, despite regular medical follow-up and targeted dietary advice for the management of CD and associated AD, three patients encountered difficulties in following the recommended diet.
CONCLUSIONS: Younger patients with CD have an increased risk of hypothyroidism and insulin-dependent diabetes. These data necessitate improved surveillance to discover these illnesses as early as possible in order to optimize management and reduce related consequences.

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OBJECTIVE: The clinical presentation of celiac disease (CD) has changed over time with more patients presenting with non-classical symptoms, extra-intestinal manifestations (EIM) or no symptoms. We aimed to investigate the main symptoms/signs leading to the diagnosis of CD in adult patients. As secondary end-point, we evaluated the outcome of gastrointestinal (GI) symptoms following gluten-free diet (GFD).
METHODS: All consecutive CD adult patients referring to our University Hospital from September 2022 to February 2024 were included. Clinical data were retrospectively evaluated.
RESULTS: 134 patients, 104 females/30 males, median age at diagnosis 35 years, were included. 79 patients reported GI symptoms (i.e., diarrhea, abdominal bloating, dyspepsia) as the main symptom leading to CD diagnosis. In 40 patients, the leading symptom/sign was an EIM (i.e., iron deficiency anemia, infertility/miscarriages, dermatitis, osteoporosis, elevated transaminase levels). Fifteen patients were asymptomatic, being diagnosed because of a positive family history or concomitant autoimmune hypothyroidism. Of the 79 patients reporting GI symptoms, 20 did not experience complete resolution with the GFD. Among the 17 patients who reported a strict adherence to GFD (vs 1 patient with low-adherence, 2 non-compliant), lactose intolerance and irritable bowel syndrome overlap were diagnosed in 2 and 15 patients, respectively.
CONCLUSIONS: GI manifestations remain the main symptoms at presentation of CD, however clinicians should be aware of the EIM of CD and the association with other autoimmune disorders. In non-responsive CD patients, an overlap with functional disorders might be considered.

OBJECTIVE: The environmental factors, apart from gluten ingestion predisposing to coeliac disease are poorly known. Smoking is associated with many immune-mediated diseases, but research on coeliac disease is scarce. This study aims to investigate how smoking affects the clinical presentation, presence of comorbidities and response to gluten-free diet in coeliac disease.
METHODS: Altogether 815 adults with coeliac disease participated in a nationwide cross-sectional study. Participants were interviewed and smoking habits (never, former, or current smoker), clinical presentation of coeliac disease and presence of comorbidities were elicited. Serology and severity of small bowel mucosal lesions at diagnosis were gathered from the participants\' medical records and follow-up serology was measured. Gastrointestinal symptoms and psychological well-being were assessed using validated questionnaires.
RESULTS: Current smokers were more often male and were diagnosed at younger ages than never or former smokers. There were no differences between the groups in clinical presentation, severity of symptoms or mucosal lesions at diagnosis or in dietary compliance and clinical, serological, and histological recovery. Musculoskeletal disorders, particularly osteoporosis and osteopenia, were more common in never smokers than in other groups (14.5% vs. 5.1% and 4.1%, p<0.001), and cardiovascular disorders were diagnosed more often in former smokers (36.2% vs. 23.5% and 21.9%, p=0.003).
CONCLUSIONS: Smoking does not seem to have an impact on the clinical presentation, severity of symptoms or mucosal damage in coeliac disease. Histological and clinical recovery as well as seroconversion on gluten-free diet are not affected by smoking status.

Celiac Disease (CD) is the most common hereditarily-based food intolerance worldwide and a chronic inflammatory condition. The current standard treatment for CD involves strict observance and compliance with a gluten-free diet (GFD). However, maintaining a complete GFD poses challenges, necessitating the exploration of alternative therapeutic approaches. Nutraceuticals, bioactive products bridging nutrition and pharmaceuticals, have emerged as potential candidates to regulate pathways associated with CD and offer therapeutic benefits. Despite extensive research on nutraceuticals in various diseases, their role in CD has been relatively overlooked. This review proposes comprehensively assessing the potential of different nutraceuticals, including phytochemicals, fatty acids, vitamins, minerals, plant-based enzymes, and dietary amino acids, in managing CD. Nutraceuticals exhibit the ability to modulate crucial CD pathways, such as regulating gluten fragment accessibility and digestion, intestinal barrier function, downregulation of tissue transglutaminase (TG2), intestinal epithelial morphology, regulating innate and adaptive immune responses, inflammation, oxidative stress, and gut microbiota composition. However, further investigation is necessary to fully elucidate the underlying cellular and molecular mechanisms behind the therapeutic and prophylactic effects of nutraceuticals for CD. Emphasizing such research would contribute to future developments in CD therapies and interventions.