Search Results (14)

Non-celiac villous atrophy (NCVA) is a multifaceted and under-recognized clinical entity with an etiology beyond celiac disease. This review critically examines the diverse pathophysiological mechanisms underlying NCVA, including autoimmune enteropathies, immune deficiency-related disorders, infectious processes, drug-induced trauma, and metabolic or environmental influences. A comprehensive synthesis of peer-reviewed literature, clinical studies, and case reports was conducted, adopting a multidisciplinary perspective that integrates immunologic, infectious, metabolic, and pharmacologic insights. The literature search was performed in three phases: identification of relevant studies, critical assessment of selected publications, and synthesis of key findings. Searches were carried out in PubMed, Scopus, Web of Science, and Google Scholar databases. The final search, completed in June 2025, included international, English-language articles, electronic books, and online reports. Studies were included if they addressed NCVA in the context of pathophysiology, clinical manifestations, or management strategies, with priority given to publications from the last ten years (2015–2025). The search strategy used the primary term “non-celiac villous atrophy” combined with supplementary keywords such as autoimmune enteropathy, common variable immunodeficiency, tropical sprue, drug-related enteropathy, pathophysiology, immunological mechanisms, chronic inflammation, genetic factors, environmental influences, and clinical management. Histopathological evaluations reveal that NCVA often manifests with varying degrees of villous blunting, crypt hypertrophy, and intraepithelial lymphocytosis, albeit without the gliadin-specific immune response seen in celiac disease. Various immune pathways are involved, such as autoimmune deregulation and chronic inflammatory responses, while drug-induced and environmental factors further complicate its clinical picture. These findings highlight significant diagnostic challenges and underscore the need to adapt diagnostic algorithms that combine clinical history, serologic evaluations, and histopathologic analysis. In conclusion, an in-depth understanding of the heterogeneous etiology of NCVA is critical to improving diagnostic accuracy and optimizing therapeutic strategies. Future research should prioritize the identification of specific biomarkers and the development of targeted interventions to address the unique mechanisms underlying NCVA, thereby improving patient management and outcomes. Full article

This review is dedicated to exploring recent advancements in the study of amaranth grain and presents research primarily on Amaranthus species such as Amaranthus cruentus, Amaranthus hypochondriacus, and Amaranthus caudatus, and to a lesser extent Amaranthus hybridus, Amaranthus mantegazzianus, Amaranthus muricatus, Amaranthus tuberculatus, Amaranthus viridis, Amaranthus spinosus, and Amaranthus tenuifoliu. Amaranth (Amaranthus spp.) is a promising, high-yield pseudocereal crop with significant commercial potential for developing functional food products. It contains a wide range of bioactive compounds, including squalene, tocopherols, phenolic compounds, phytates, and vitamins, which possess important physiological properties. Amaranth grain is characterized by high levels of starch, proteins, minerals, and dietary fiber. Moreover, amaranth proteins are distinguished by a balanced amino acid composition and exhibit greater resistance to external factors compared to animal-derived proteins. Grains of amaranth are free of gliadin, making it a valuable nutritional source for individuals with celiac disease, an immune-mediated disorder. Unlike traditional cereals, where prolamins and glutelins dominate the protein composition, the proteins of pseudocereals like amaranth primarily consist of albumins and globulins. The processing methods of amaranth grain influence their quantitative and qualitative composition, often significantly improving their physicochemical, antioxidant, functional, and rheological properties. This work provides a detailed analysis of amaranth’s chemical composition and bioactive components, along with its evaluation of therapeutic and preventive properties. Amaranth protein fractions (albumin, globulin, and glutelin) and squalene exhibit increased antioxidant activity, contributing to notable resistance to radiation and X-ray exposure. Bioactive compounds such as phytol, α-tocopherol, and a lunasin-like peptide (AhLun) with potential anticancer properties have also been identified in amaranth. Furthermore, six bioactive peptides were isolated and identified from amaranth, which, according to predictive models, demonstrate a high capacity to inhibit angiotensin-converting enzyme (ACE) activity, suggesting potential hypotensive effects. Certain amaranth peptides are considered promising functional food ingredients for the prevention and comprehensive treatment of conditions such as diabetes, inflammatory bowel diseases, hypercholesterolemia, cardiovascular diseases, and obesity. Amaranthus spp. and its processed products hold significant interest for the development of innovative food products, contributing to the expansion of their range and enhancement of nutritional value. Full article

Celiac disease is defined as a systemic immunological disorder caused by gluten (gliadin and other prolamin) in genetically predisposed individuals, who present with a variety of gluten-dependent symptoms, specific antibodies, the presence of the HLA DQ2 and DQ8 histocompatibility antigen, and enteropathy. Its prevalence, depending on the studied population and methodology, is estimated at 0.75–1.6% of the general population. During the complex immune reaction it induces, most cells involved in inflammatory processes are activated, which leads to the gradual atrophy of intestinal villi and the proliferation of enterocytes within intestinal crypts. The pathogenesis of celiac disease is extremely complicated and is still the subject of research. According to the current diagnostic guidelines, the following criteria should be taken into account: clinical symptoms (intestinal and extraintestinal), the presence of antibodies against tissue transglutaminase in the IgA class, the level of total IgA, and the presence of typical histological changes in duodenal biopsies. Diet-resistant celiac disease is one of the most important clinical challenges, causing serious complications. Currently, the basic method for treating celiac disease is an elimination diet (i.e., the exclusion of products that may contain gluten from the diet), however, new therapeutic strategies are still being sought, mainly based on supplementation with exogenous endopeptidases, modification of the immune response, and the use of zonulin inhibitors and transglutaminase 2 inhibitors. Clinical trials of new drugs are ongoing. The gradually expanding knowledge about the pathogenesis of celiac disease may allow for the development of new therapeutic strategies for both patients with a mild disease course, as well as those that are diet-resistant. Full article

Celiac disease (CD) is a common systemic disorder that results from an abnormal response of human immunity to gluten intake, affecting the small intestine. In individuals who carry a genetic susceptibility, CD is triggered by environmental factors, including viral infections and dysbiosis of the gut microbiota. The gut microbiome is essential in controlling the immune system, and recent findings indicate that changes in the gut microbiome may contribute to various chronic immune disorders, such as CD through mechanisms that still require further exploration. Some bacteria exhibit epitopes that mimic gliadin and may enhance an immune response in the host. Other bacteria, including Pseudomonas aeruginosa, may work in conjunction with gluten to trigger and escalate intestinal inflammation. The microbiota may also directly influence antigen development through the production of immunogenic or tolerogenic gluten peptides or directly influence intestinal permeability through the release of zonulin. Finally, the gut microbiome can impact intestinal inflammation by generating proinflammatory or anti-inflammatory cytokines and metabolites. It is crucial to consider the impact of genetic factors (specifically, HLA-DQ haplotypes), perinatal elements such as birth mode, type of infant feeding, and antibiotic and infection exposure on the composition of the early intestinal microbiome. According to the available studies, the gut microbiome alterations associated with CD tend to exhibit a decreased presence of beneficial bacteria, including some anti-inflammatory Bifidobacterium species. However, some controversy remains as some reports have found no significant differences between the gut microbiomes of individuals with and without CD. A better understanding of the gut microbiome’s role in the development of CD would greatly benefit both prevention and treatment efforts, especially in complicated or treatment-resistant cases. Here, we have attempted to summarize the available evidence on the relationship between the gut microbiota and CD, with a particular focus on potential therapeutic targets. Full article

Gliadins proteins make up around 30% of total wheat flour proteins. They are involved in many immune disorders affecting an increasing number of people who eat foods made with wheat flour. The triggering factor is the accumulation in the gut of immunogenic peptides derived from incomplete degradation of gliadins by gastric proteases. Previous research has revealed the effectiveness of sourdough-fermentation technology or related lactic acid bacteria in reducing wheat flour allergenic proteins. However, there are no single yeast cultures for producing reduced allergenicity wheat products. This study evaluated sourdough-related yeast Wickerhamomyces anomalus strains for their ability to hydrolyze gliadin proteins. All yeast strains were able to degrade gliadins and use them as carbon and nitrogen sources. The proliferation of the yeast strains depended on the gliadin addition; complete hydrolysis was observed after 24 h. The strain showing higher proteolytic activity fermented, acceptably wheat flour dough. The gliadin content of the leavened dough was reduced by 50%. Bread made from the W. anomalus-fermented dough showed a 78% reduction in immunogenic α-gliadins. 50% of the decrease was attributed to the proteolytic activity of the yeast cells, and the other 35% to the baking process. These results show the potential of the yeast W. anomalus as a starter for reducing immunogenicity wheat products. Full article

Celiac disease (CeD) is a conditional autoimmune disorder with T cell-mediated immune response to gluten coupled with antibody production to gliadin and the self-protein tissue transglutaminase (TG2). TG2 contributes to the CeD pathomechanism by deamidating gliadin, thereby generating more immunogenic peptides. Anti-gliadin antibodies may appear before the autoantibody production. The scope of this study was to dissect these early antibody responses by investigating serum samples collected during the PreventCD prospective double-blind study, where infants with high CeD risk were randomized to 200 mg daily gluten intake or placebo from 4 to 6 months of age, followed by frequent blood testing on regular gluten consumption in both groups. After primary gluten intake, children with or without later CeD produced IgA and IgG antibodies which preferentially recognized non-deamidated gliadin peptides. At CeD development with anti-TG2 seroconversion, there was a significant increase in the antibody reaction toward deamidated gliadin peptides (DGP), with maturation in the binding strength for the PEQPFP gamma-gliadin core peptide. The earliest produced autoantibodies targeted TG2’s celiac epitope 2. Our results reveal a qualitative change in the gliadin-directed humoral immune response at the time when anti-TG2 antibodies appear, but anti-DGP antibodies in the absence of anti-TG2 antibodies are not disease-predictive. Full article

Celiac disease (CD) is a genetically predisposed, T cell-mediated and autoimmune-like disorder caused by dietary exposure to the storage proteins of wheat and related cereals. A gluten-free diet (GFD) is the only treatment available for CD. The celiac immune response mediated by CD4+ T-cells can be assessed with a short-term oral gluten challenge. This study aimed to determine whether the consumption of bread made using flour from a low-gluten RNAi wheat line (named E82) can activate the immune response in DQ2.5-positive patients with CD after a blind crossover challenge. The experimental protocol included assessing IFN-γ production by peripheral blood mononuclear cells (PBMCs), evaluating gastrointestinal symptoms, and measuring gluten immunogenic peptides (GIP) in stool samples. The response of PBMCs was not significant to gliadin and the 33-mer peptide after E82 bread consumption. In contrast, PBMCs reacted significantly to Standard bread. This lack of immune response is correlated with the fact that, after E82 bread consumption, stool samples from patients with CD showed very low levels of GIP, and the symptoms were comparable to those of the GFD. This pilot study provides evidence that bread from RNAi E82 flour does not elicit an immune response after a short-term oral challenge and could help manage GFD in patients with CD. Full article

Gluten-related disorders (GRDs) are a group of diseases that involve the activation of the immune system triggered by the ingestion of gluten, with a worldwide prevalence of 5%. Among them, Celiac disease (CeD) is a T-cell-mediated autoimmune disease causing a plethora of symptoms from diarrhea and malabsorption to lymphoma. Even though GRDs have been intensively studied, the environmental triggers promoting the diverse reactions to gluten proteins in susceptible individuals remain elusive. It has been proposed that pathogens could act as disease-causing environmental triggers of CeD by molecular mimicry mechanisms. Additionally, it could also be possible that unrecognized molecular, structural, and physical parallels between gluten and pathogens have a relevant role. Herein, we report sequence, structural and physical similarities of the two most relevant gluten peptides, the 33-mer and p31-43 gliadin peptides, with bacterial pathogens using bioinformatics going beyond the molecular mimicry hypothesis. First, a stringent BLASTp search using the two gliadin peptides identified high sequence similarity regions within pathogen-derived proteins, e.g., extracellular proteins from Streptococcus pneumoniae and Granulicatella sp. Second, molecular dynamics calculations of an updated α-2-gliadin model revealed close spatial localization and solvent-exposure of the 33-mer and p31-43 peptide, which was compared with the pathogen-related proteins by homology models and localization predictors. We found putative functions of the identified pathogen-derived sequence by identifying T-cell epitopes and SH3/WW-binding domains. Finally, shape and size parallels between the pathogens and the superstructures of gliadin peptides gave rise to novel hypotheses about activation of innate immunity and dysbiosis. Based on our structural findings and the similarities with the bacterial pathogens, evidence emerges that these pathologically relevant gluten-derived peptides could behave as non-replicating pathogens opening new research questions in the interface of innate immunity, microbiome, and food research. Full article

Celiac disease (CD) is a chronic immune-mediated enteropathy triggered by exposure to dietary gluten in genetically predisposed individuals. In contrast, irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder affecting the large intestine, without an autoimmune component. Here, we evaluated the prevalence of IgA and IgG antibodies to maize zeins (AZA) in patients with CD and IBS. Using an in-house ELISA assay, the IgA and IgG anti-zein antibodies in the serum of 37 newly diagnosed CD (16 biopsy proved and 21 serological diagnosis) and 375 IBS patients or 302 healthy control (HC) subjects were measured. Elevated levels of IgA AZA were found in CD patients compared with IBS patients (p < 0.01) and HC (p < 0.05). CD patients had the highest prevalence (35.1%), followed by IBS (4.3%) and HCs (2.3%) (p < 0.0001). IgG AZA antibodies were not found in any CD patients, IBS patients, or HC subjects. A significant positive correlation was found between IgA AZA with IgA anti-gliadin (AGA, r = 0.34, p < 0.01) and IgA anti-deaminated gliadin peptides (DGP, r = 0.42, p < 0.001) in the celiac disease group. Taken together, our results show for the first time a higher prevalence of AZA IgA antibodies in newly diagnosed CD patients than in IBS patients, confirming a biased immune response to other gliadin-related prolamins such as maize zeins in genetically susceptible individuals. Full article

Schizophrenia is a heterogeneous disorder without a fully elucidated etiology and mechanisms. One likely explanation for the development of schizophrenia is low-grade inflammation, possibly caused by processes in the gastrointestinal tract related to gluten sensitivity. The aims of this study were to: (1) compare levels of markers of gluten sensitivity, inflammation and gut permeability, and (2) determine associations between gluten sensitivity, inflammation, and intestinal permeability in patients with first-episode/chronic (FS/CS) schizophrenia and healthy individuals (HC). The total sample comprised 162 individuals (52 FS; 50 CS, and 60 HC). The examination included clinical variables, nutritional assessment, and serum concentrations of: high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), soluble CD14 (sCD14), anti-Saccharomyces cerevisiae antibody (ASCA), antigliadin antibodies (AGA) IgA/IgG, antibodies against tissue transglutaminase 2 (anti-tTG) IgA, anti-deamidated gliadin peptides (anti-DGP) IgG. A significant difference between groups was found in sCD14, ASCA, hs-CRP, IL-6 and AGA IgA levels. AGA IgG/IgA levels were higher in the FS (11.54%; 30.77%) and CS (26%; 20%) groups compared to HC. The association between intestinal permeability and inflammation in the schizophrenic patients only was noted. The risk for developing schizophrenia was odds ratio (OR) = 4.35 (95% confidence interval (CI 1.23–15.39) for AGA IgA and 3.08 (95% CI 1.19–7.99) for positive AGA IgG. Inflammation and food hypersensitivity reactions initiated by increased intestinal permeability may contribute to the pathophysiology of schizophrenia. The immune response to gluten in FS differs from that found in CS. Full article

Celiac Disease (CD) is an immune-mediated disease triggered by the ingestion of wheat gliadin and related prolamins from other cereals, such as barley and rye. Immunity against these cereal-derived proteins is mediated by pro-inflammatory cytokines produced by both innate and adaptive system response in individuals unable to adequately digest them. Peptides generated in this condition are absorbed across the gut barrier, which in these patients is characterized by the deregulation of its permeability. Here, we discuss a possible correlation between CD and Autistic Spectrum Disorder (ASD) pathogenesis. ASD can be induced by an excessive and inappropriate brain opioid activity during the neonatal period. Cereal-derived peptides produced in celiac patients cross the blood–brain barrier and bind to endogenous opioid receptors interfering with neurotransmission and generating deleterious effects on brain maturation, learning and social relations. Moreover, an increase in oxidative stress and a decrease in the antioxidant capacity, as well as an extended mitochondrial impairment in the brain, could represent a possible connection between ASD and CD. Therefore, we critically discuss the proposed relationship between ASD and CD and the possible usefulness of a gluten-free diet in ASD patients. Full article

Celiac disease (CD) is a chronic systemic autoimmune disorder that is triggered by the ingestion of gliadin peptides, the alcohol-soluble fraction of wheat gluten. These peptides, which play a key role in the immune response that underlies CD, spontaneously form aggregates and exert a direct toxic action on cells due to the increase in the reactive oxygen species (ROS) levels. Furthermore, peptic-tryptic digested gliadin peptides (PT-gliadin) lead to an impairment in the autophagy pathway in an in vitro model based on Caco-2 cells. Considering these premises, in this study we have analyzed different mTOR-independent inducers, reporting that the disaccharide trehalose, a mTOR-independent autophagy activator, rescued the autophagy flux in Caco-2 cells treated with digested gliadin, as well as improved cell viability. Moreover, trehalose administration to Caco-2 cells in presence of digested gliadin reduced the intracellular levels of these toxic peptides. Altogether, these results showed the beneficial effects of trehalose in a CD in vitro model as well as underlining autophagy as a molecular pathway whose modulation might be promising in counteracting PT-gliadin cytotoxicity. Full article

Celiac disease (CD) is a chronic immune-mediated disorder, characterized by enhanced paracellular permeability across the intestinal epithelium. The complex system of intercellular junctions, including tight junctions (TJs) and adherens junctions (AJs), seals together the epithelial cells to form a continuous layer. The improvements in barrier integrity have been related to modifications in intercellular junction protein expression. Polyamines (spermidine, spermine, and putrescine) actively participate in the modulation of the AJ expression. Both in vitro and in vivo studies have demonstrated that also probiotics can promote the integrity and the function of the intestinal barrier. On these bases, the present work investigated the protective effects exerted by Lactobacillus rhamnosus GG (L.GG) against the pepsin-trypsin-digested gliadin (PTG)-induced enteropathy in jejunal tissue samples of Wistar rats. In particular, the probiotic effects have been evaluated on the intestinal mucosal architecture, polyamine metabolism and intercellular junction protein expression (ZO-1, Occludin, Claudin-1, β-catenin and E-cadherin). The results from this study indicate that L.GG protects the intestinal mucosa of rats from PTG-induced damage, by preventing the reduction of the expression of the intercellular junction proteins. Consequently, a role for L.GG in the therapeutic management of the gluten-related disorders in humans could be hypothesized. Full article

Celiac disease (CD) is an immune-mediated disorder caused by the ingestion of wheat gluten. A lifelong, gluten-free diet is required to alleviate symptoms and to normalize the intestinal mucosa. We previously found that transamidation reaction by microbial transglutaminase (mTG) was effective in down-regulating the gliadin-specific immune response in CD patients. In this study, the two-step transamidation protocol was adopted to treat commercial wheat semolina on a pilot scale. The effectiveness of the enzymatic reaction was tested by means of consolidated biochemical and immunological methods on isolated prolamins. We found that water-insoluble gliadin and glutenin yields decreased in wheat semolina to 5.9% ± 0.3% and 11.6% ± 0.1%, respectively, after a two-step transamidation reaction. Using DQ8 transgenic mice as a model of gluten sensitivity, we observed a dramatic reduction in IFN-γ production in spleen cells challenged in vitro with the residual insoluble gliadin from transamidated semolina (N = 6; median values: 850 vs. 102; control vs. transamidated semolina, p < 0.05). The technological properties of treated wheat semolina were then tested by manufacturing classical pasta (spaghetti). Notably, the spaghetti manufactured with transamidated semolina had only minor changes in its features before and after cooking. In conclusion, the two-step transamidation reaction modified the immunogenic epitopes of gliadins also on a pilot-scale level without influencing the main technological properties of semolina. Our data shed further light on a detoxification strategy alternative to the current gluten-free diet and may have important implications for the management of CD patients. Full article