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Keywords = Non-celiac gluten sensitivity

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33 pages, 799 KiB  
Review
The Ten Dietary Commandments for Patients with Irritable Bowel Syndrome: A Narrative Review with Pragmatic Indications
by Nicola Siragusa, Gloria Baldassari, Lorenzo Ferrario, Laura Passera, Beatrice Rota, Francesco Pavan, Fabrizio Santagata, Mario Capasso, Claudio Londoni, Guido Manfredi, Danilo Consalvo, Giovanni Lasagni, Luca Pozzi, Vincenza Lombardo, Federica Mascaretti, Alice Scricciolo, Leda Roncoroni, Luca Elli, Maurizio Vecchi and Andrea Costantino
Nutrients 2025, 17(15), 2496; https://doi.org/10.3390/nu17152496 - 30 Jul 2025
Viewed by 581
Abstract
Irritable bowel syndrome (IBS) is a gut–brain axis chronic disorder, characterized by recurrent abdominal pain and altered bowel habits in the absence of organic pathology. Nutrition plays a central role in symptom management, yet no single dietary strategy has demonstrated universal effectiveness. This [...] Read more.
Irritable bowel syndrome (IBS) is a gut–brain axis chronic disorder, characterized by recurrent abdominal pain and altered bowel habits in the absence of organic pathology. Nutrition plays a central role in symptom management, yet no single dietary strategy has demonstrated universal effectiveness. This narrative review critically evaluates current nutritional approaches to IBS. The low-Fermentable Oligo-, Di-, Mono-saccharides and Polyols (FODMAP) diet is the most extensively studied and provides short-term symptom relief, but its long-term effects on microbiota diversity remain concerning. The Mediterranean diet, due to its anti-inflammatory and prebiotic properties, offers a sustainable, microbiota-friendly option; however, it has specific limitations in the context of IBS, particularly due to the adverse effects of certain FODMAP-rich foods. A gluten-free diet may benefit individuals with suspected non-celiac gluten sensitivity, although improvements are often attributed to fructan restriction and placebo and nocebo effects. Lactose-free diets are effective in patients with documented lactose intolerance, while a high-soluble-fiber diet is beneficial for constipation-predominant IBS. IgG-based elimination diets are emerging but remain controversial and require further validation. In this review, we present the 10 dietary commandments for IBS, pragmatic and easily retained recommendations. It advocates a personalized, flexible, and multidisciplinary management approach, avoiding rigidity and standardized protocols, with the aim of optimizing adherence, symptom mitigation, and health-related quality of life. Future research should aim to evaluate, in real-world clinical settings, the impact and applicability of the 10 dietary commandments for IBS in terms of symptom improvement and quality of life Full article
(This article belongs to the Special Issue Dietary Interventions for Functional Gastrointestinal Disorders)
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16 pages, 1309 KiB  
Review
Microbial Peptidases: Key Players in Reducing Gluten Immunogenicity Through Peptide Degradation
by Africa Sanchiz, M. Isabel San-Martín, N. Navasa, Honorina Martínez-Blanco, Miguel Ángel Ferrero, Leandro Benito Rodríguez-Aparicio and Alejandro Chamizo-Ampudia
Appl. Sci. 2025, 15(14), 8111; https://doi.org/10.3390/app15148111 - 21 Jul 2025
Viewed by 275
Abstract
Gluten-related disorders, including celiac disease (CeD) and non-celiac gluten sensitivity (NCGS), are triggered by the immune response to gluten peptides that resist complete digestion by human gastrointestinal enzymes. Microbial peptidases have emerged as promising biocatalysts capable of degrading these immunogenic peptides, offering potential [...] Read more.
Gluten-related disorders, including celiac disease (CeD) and non-celiac gluten sensitivity (NCGS), are triggered by the immune response to gluten peptides that resist complete digestion by human gastrointestinal enzymes. Microbial peptidases have emerged as promising biocatalysts capable of degrading these immunogenic peptides, offering potential therapeutic and industrial applications. This review explores the role of microbial peptidases in gluten degradation, highlighting key enzyme families, their mechanisms of action, and their effectiveness in reducing gluten immunogenicity. Additionally, we discuss advances in enzymatic therapy, food processing applications, and the challenges associated with optimizing microbial enzymes for safe and efficient gluten detoxification. Understanding the potential of microbial peptidases in mitigating gluten-related disorders paves the way for novel dietary and therapeutic strategies. Full article
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27 pages, 3370 KiB  
Review
Sourdough Fermentation and Gluten Reduction: A Biotechnological Approach for Gluten-Related Disorders
by Ricardo H. Hernández-Figueroa, Aurelio López-Malo and Emma Mani-López
Microbiol. Res. 2025, 16(7), 161; https://doi.org/10.3390/microbiolres16070161 - 17 Jul 2025
Viewed by 623
Abstract
Sourdough fermentation has emerged as a promising biotechnological approach to reducing gluten content and modifying gluten proteins in wheat-based products. This review assesses the current scientific literature on the enzymatic degradation and hydrolysis of gluten during lactic acid bacteria (LAB) sourdough fermentation. It [...] Read more.
Sourdough fermentation has emerged as a promising biotechnological approach to reducing gluten content and modifying gluten proteins in wheat-based products. This review assesses the current scientific literature on the enzymatic degradation and hydrolysis of gluten during lactic acid bacteria (LAB) sourdough fermentation. It explores implications for individuals with gluten-related disorders, including celiac disease, non-celiac gluten sensitivity and intolerance, as well as irritable bowel syndrome (IBS). In addition, LAB sourdough effect on fermentable oligo-, di-, monosaccharides and polyols (FODMAPs), amylase-trypsin inhibitors (ATIs), and phytate are revised. Selected homo- and heterofermentative LAB are capable of degrading gluten proteins, especially the polypeptides derived from the action of native cereal proteases. Mixed cultures of LAB degrade gluten peptides more effectively than monocultures. However, LAB sourdough is not sufficient to remove the toxic peptides to the minimal level (<20 ppm). This goal is achieved only if sourdough is combined with fungal proteases during sourdough fermentation. LAB sourdough directly contributes to lower FODMAPs but not ATIs and phytate. Phytate is reduced by the endogenous cereal phytases activated at acidic pHs (pH < 5.0), conditions generated during sourdough fermentation. ATIs are also lowered by endogenous cereal proteases instead of LAB proteases/peptidases. Despite LAB sourdough not fully degrading the gluten or directly reducing the ATIs and phytate, it participates through peptidases activity and acidic pH that trigger the action of endogenous cereal proteases and phytases. Full article
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22 pages, 52413 KiB  
Systematic Review
Micronutrient Deficiencies Associated with a Gluten-Free Diet in Patients with Celiac Disease and Non-Celiac Gluten or Wheat Sensitivity: A Systematic Review and Meta-Analysis
by Lindsey A. Russell, Paige Alliston, David Armstrong, Elena F. Verdu, Paul Moayyedi and Maria Ines Pinto-Sanchez
J. Clin. Med. 2025, 14(14), 4848; https://doi.org/10.3390/jcm14144848 - 8 Jul 2025
Viewed by 597
Abstract
Background: A gluten-free diet (GFD) has been shown to be nutritionally inadequate for those with wheat-related disorders. However, the differences in findings and the absence of quantitative analysis limits the interpretation of previous reviews. Objectives: We conducted a systematic review and meta-analysis to [...] Read more.
Background: A gluten-free diet (GFD) has been shown to be nutritionally inadequate for those with wheat-related disorders. However, the differences in findings and the absence of quantitative analysis limits the interpretation of previous reviews. Objectives: We conducted a systematic review and meta-analysis to identify the risk of micronutrient deficiencies in patients with celiac disease (CeD) and non-celiac gluten or wheat sensitivity (NCWS). Methods: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, and Web of Science (Ovid) databases. The risk of bias was determined using the ROBINS-1, and the quality of evidence was assessed using the GRADE approach. Results We identified 7940 studies; 46 observational studies (11 cohort, 9 cross-sectional, and 26 case–control) were eligible for analysis. CeD patients had an increased risk of vitamin D and E deficiencies compared with the non-CeD controls. CeD on a GFD had a decreased risk of vitamin D, B12, E, calcium, and iron deficiencies compared with untreated CeD. NCWS had an increased risk of vitamin B12, folate, and iron deficiency compared to the controls. The overall quality of evidence was rated very low. Conclusions: The risk of various micronutrient deficiencies is increased in CeD but is decreased for some after a GFD. Adequately powered studies with a rigorous methodology are needed to inform the risk of nutrient deficiencies in patients with CeD and NCWS. Protocol registration: Prospero-CRD42022313508. Full article
(This article belongs to the Special Issue Future Trends in the Diagnosis and Management of Celiac Disease)
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16 pages, 600 KiB  
Review
Reproductive Health and Assisted Conception in Celiac Disease and Non-Celiac Gluten Sensitivity: A Narrative Review
by Efthalia Moustakli, Panagiotis Christopoulos, Anastasios Potiris, Athanasios Zikopoulos, Eirini Drakaki, Theodoros Karampitsakos, Ismini Anagnostaki, Nikolaos Kathopoulis, Periklis Katopodis, Apostolia Galani, Chrysi Christodoulaki, Athanasios Zachariou, Peter Drakakis and Sofoklis Stavros
Nutrients 2025, 17(13), 2215; https://doi.org/10.3390/nu17132215 - 3 Jul 2025
Viewed by 673
Abstract
The increasing use of assisted reproductive technologies (ARTs) globally, such as intracytoplasmic sperm injection (ICSI) and in vitro fertilization (IVF), has highlighted the pressing need to determine the modifiable factors affecting the success of implantation and the outcomes of early pregnancy. Scientific interest [...] Read more.
The increasing use of assisted reproductive technologies (ARTs) globally, such as intracytoplasmic sperm injection (ICSI) and in vitro fertilization (IVF), has highlighted the pressing need to determine the modifiable factors affecting the success of implantation and the outcomes of early pregnancy. Scientific interest in the role of nutrition in fertility is growing, but outside of celiac disease, little is known about gluten, a dietary protein with immunogenic and inflammatory properties. With an emphasis on ART results, this narrative review summarizes the most recent data regarding the possible effects of gluten consumption on reproductive health, focusing primarily on individuals with celiac disease (CD) and non-celiac gluten sensitivity (NCGS). In addition to discussing potential molecular processes connecting gluten-induced inflammation, increased gut permeability, autoimmune, and decreased endometrial receptivity, we further explore the documented link between CD and infertility and investigate new information on NCGS. These findings are tentative and based on scant low-quality evidence, although some case reports and small clinical studies have indicated that avoiding gluten may help some people undergoing ART, especially those with immune-mediated diseases or infertility that cannot be explained. There is currently no robust prospective evidence confirming that gluten restriction improves infertility outcomes. Therefore, before gluten elimination is advised in this situation, more carefully planned extensive research is required to generate reliable scientific proof. Beyond traditional celiac disease, we suggest that gluten sensitivity might be an underappreciated factor in ART failure that merits more research. A gluten-free diet may serve as a low-risk supplementary option for appropriately selected patients, pending the results of more extensive controlled studies. Full article
(This article belongs to the Special Issue Nutritional Effects on Women’s Reproductive Health and Disease)
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17 pages, 1290 KiB  
Article
Non-Celiac Wheat Gluten Sensitivity Model: Effects on Hepatic Morphophysiology of Wistar Rats
by Ana Luiza Russo Duarte, Gabriela Barone Volce da Silva, Anne Caroline Santa Rosa, Ghiovani Zanzotti Raniero, Antonio Roberto Giriboni Monteiro, Gustavo Henrique de Souza, Anacharis Babeto de Sá-Nakanishi, Jurandir Fernando Comar, Roberto Kenji Nakamura Cuman and Maria Raquel Marçal Natali
Nutrients 2025, 17(11), 1842; https://doi.org/10.3390/nu17111842 - 28 May 2025
Viewed by 537
Abstract
Background/Objectives: Wheat gluten intolerance increases intestinal permeability, triggering inflammation that may directly affect liver function and compromise metabolic health. Methods: Male Wistar rats (n = 50) aged 21 days were divided into five groups (n = 10) based on dietary gluten levels over [...] Read more.
Background/Objectives: Wheat gluten intolerance increases intestinal permeability, triggering inflammation that may directly affect liver function and compromise metabolic health. Methods: Male Wistar rats (n = 50) aged 21 days were divided into five groups (n = 10) based on dietary gluten levels over 100 days: G0 (0%), G14 (14%), G42 (42%), G70 (70%), and G70/0 (70% for the first 70 days, then 0% until euthanasia). At 121 days, the animals were weighed and euthanized, and blood samples were collected for biochemical analyses. Adipose tissue deposits and the liver were excised and weighed. Liver lobes were isolated and fixed for morphological and morphometric analysis of hepatocytes, tissue glycogen percentage, and intracellular lipid assessment. Results: The hepatic oxidative status was evaluated. The ingestion of diets with excess gluten (70%) increased final body mass and reduced liver mass, though it did not alter the adiposity index. Cholesterol, triglycerides, and myeloperoxidase enzyme activity exhibited distinct patterns across all groups. Conclusions: Elevated gluten levels increased oxidative stress and altered tissue hepatic morphology and morphometry. Full article
(This article belongs to the Section Nutrition and Metabolism)
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18 pages, 7671 KiB  
Article
Automated Gluten Detection in Bread Images Using Convolutional Neural Networks
by Aviad Elyashar, Abigail Paradise Vit, Guy Sebbag, Alex Khaytin and Avi Zakai
Appl. Sci. 2025, 15(4), 1737; https://doi.org/10.3390/app15041737 - 8 Feb 2025
Cited by 1 | Viewed by 1210
Abstract
Celiac disease and gluten sensitivity affect a significant portion of the population and require adherence to a gluten-free diet. Dining in social settings, such as family events, workplace gatherings, or restaurants, makes it difficult to ensure that certain foods are gluten-free. Despite the [...] Read more.
Celiac disease and gluten sensitivity affect a significant portion of the population and require adherence to a gluten-free diet. Dining in social settings, such as family events, workplace gatherings, or restaurants, makes it difficult to ensure that certain foods are gluten-free. Despite the availability of portable gluten testing devices, these instruments have high costs, disposable capsules, depend on user preparation and technique, and cannot analyze an entire meal or detect gluten levels below the legal thresholds, potentially leading to inaccurate results. In this study, we propose RGB (Recognition of Gluten in Bread), a novel deep learning-based method for automatically detecting gluten in bread images. RGB is a decision-support tool to help individuals with celiac disease make informed dietary choices. To develop this method, we curated and annotated three unique datasets of bread images collected from Pinterest, Instagram, and a custom dataset containing information about flour types. Fine-tuning pre-trained convolutional neural networks (CNNs) on the Pinterest dataset, our best-performing model, ResNet50V2, achieved 77% accuracy and recall. Transfer learning was subsequently applied to adapt the model to the Instagram dataset, resulting in 78% accuracy and 77% recall. Finally, further fine-tuning the model on a significantly different dataset, the custom bread dataset, significantly improved the performance, achieving an accuracy of 86%, precision of 87%, recall of 86%, and F1-score of 86%. Our analysis further revealed that the model performed better on gluten-free flours, achieving higher accuracy scores for these types. This study demonstrates the feasibility of image-based gluten detection in bread and highlights its potential to provide a cost-effective non-invasive alternative to traditional testing methods by allowing individuals with celiac disease to receive immediate feedback on potential gluten content in their meals through simple food photography. Full article
(This article belongs to the Special Issue Convolutional Neural Networks and Computer Vision)
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29 pages, 642 KiB  
Review
Non-Celiac Gluten/Wheat Sensitivity—State of the Art: A Five-Year Narrative Review
by Francesca Manza, Lisa Lungaro, Anna Costanzini, Fabio Caputo, Antonio Carroccio, Pasquale Mansueto, Aurelio Seidita, Suneil A. Raju, Umberto Volta, Roberto De Giorgio, David S. Sanders and Giacomo Caio
Nutrients 2025, 17(2), 220; https://doi.org/10.3390/nu17020220 - 8 Jan 2025
Cited by 1 | Viewed by 6858
Abstract
Background: Non-celiac gluten/wheat sensitivity (NCGWS) is a syndrome for which pathogenesis and management remain debated. It is described as a condition characterized by gastrointestinal and extra-intestinal symptoms rapidly occurring after gluten ingestion in subjects who have had celiac disease or wheat allergy excluded. [...] Read more.
Background: Non-celiac gluten/wheat sensitivity (NCGWS) is a syndrome for which pathogenesis and management remain debated. It is described as a condition characterized by gastrointestinal and extra-intestinal symptoms rapidly occurring after gluten ingestion in subjects who have had celiac disease or wheat allergy excluded. To date, the diagnosis of NCGWS is challenging as no universally recognized biomarkers have been yet identified, nor has a predisposing genetic profile been described. However, the research is moving fast, and new data regarding pathogenic pathways, patients’ classification, potential candidate biomarkers, and dietary interventions are emerging. Methods: This literature review aims to address the state of the art and summarize the latest updates in this field from 2019 to date. Results and Conclusions: Clinical studies regarding NCGWS in the last five years are reported to shed light on this complex condition and to guide specialists towards a more in-depth, prompt, and objective diagnosis. Full article
(This article belongs to the Section Nutritional Immunology)
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13 pages, 3486 KiB  
Review
Gluten-Free Diet for Fashion or Necessity? Review with New Speculations on Irritable Bowel Syndrome-like Disorders
by Raffaele Borghini, Alessia Spagnuolo, Giuseppe Donato and Giovanni Borghini
Nutrients 2024, 16(23), 4236; https://doi.org/10.3390/nu16234236 - 8 Dec 2024
Cited by 1 | Viewed by 2896
Abstract
Nowadays, the gluten-free diet (GFD) has become much more than the dietary treatment for celiac disease. Due to its presumed beneficial effects even in non-celiac subjects, it has become a new fashion statement and it is promoted by some healthcare professionals, social media [...] Read more.
Nowadays, the gluten-free diet (GFD) has become much more than the dietary treatment for celiac disease. Due to its presumed beneficial effects even in non-celiac subjects, it has become a new fashion statement and it is promoted by some healthcare professionals, social media and marketing strategists. On the other hand, regardless of a proper medical indication, a GFD may present side effects, such as poor palatability, high costs and socio-psychological adversities. Moreover, it can be an obstacle to correct clinical practice and may induce nutritional deficiency due to a low-quality diet. In addition, a GFD can trigger or exacerbate many irritable bowel syndrome (IBS)-like disorders in predisposed subjects: reactivity to dietary nickel, the increased consumption of FODMAP-rich foods and histamine intolerance seem to frequently play a relevant role. The possible intersections between high-risk foods in these categories of patients, as well as the possible overlaps among IBS-like disorders during GFD, are described. In conclusion, it is advisable to undergo a careful clinical evaluation by a gastroenterologist and a nutritionist (in some cases, also a psychotherapist) before starting and during a GFD, because both benefits and risks are possible. It is also important to take into account IBS-like disorders that can be exacerbated by a GFD and that are still underestimated today. Full article
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7 pages, 215 KiB  
Communication
FODMAP Diet in Celiac Disease and Gluten-Related Disorders
by Paolo Usai Satta, Giammarco Mocci and Mariantonia Lai
Nutrients 2024, 16(23), 4190; https://doi.org/10.3390/nu16234190 - 4 Dec 2024
Cited by 4 | Viewed by 1914
Abstract
Background: Individuals with celiac disease (CD) often report the persistence of gastrointestinal symptoms despite adherence to a gluten-free diet (GFD). A diet rich in fermentable oligo-, di-, and monosaccharides and polyols (FODMAPs) could cause symptoms in CD on a GFD, and conversely a [...] Read more.
Background: Individuals with celiac disease (CD) often report the persistence of gastrointestinal symptoms despite adherence to a gluten-free diet (GFD). A diet rich in fermentable oligo-, di-, and monosaccharides and polyols (FODMAPs) could cause symptoms in CD on a GFD, and conversely a low-FODMAP diet could positively influence the therapeutic management of CD and non-celiac gluten sensitivity (NCGS). The aim of this review was to explore the hypothetical impact of the FODMAD diet and the low-FODMAP diet (LFD) in CD and gluten-related disorders. Methods: A complete online search for FODMAP related to CD, NCGS, and the GFD was carried out using the Pubmed, Medline, and Cochrane databases. Results: Indeed, an LFD could successfully provide symptom relief in GFD-treated CD patients. Fructans, typical components of FODMAPs, have been associated with digestive symptoms in NCGS, and an LFD could improve the clinical picture. According to some evidence, an LFD could also improve the psychological status both in celiac patients on a GFD and in NCGS. However, an LFD should not have a significant impact on gut microbiota. Conclusions: Recent evidence supports the role of FODMAP restriction in CD patients with persistent symptoms on a GFD and in decreasing gastrointestinal disturbances in NCGS, although the GFD still represents the first-line therapy. Full article
35 pages, 2915 KiB  
Review
Gluten Unraveled: Latest Insights on Terminology, Diagnosis, Pathophysiology, Dietary Strategies, and Intestinal Microbiota Modulations—A Decade in Review
by Dana Stanciu, Hristian Staykov, Stela Dragomanova, Lyubka Tancheva, Radu Samuel Pop, Irina Ielciu and Gianina Crișan
Nutrients 2024, 16(21), 3636; https://doi.org/10.3390/nu16213636 - 25 Oct 2024
Cited by 5 | Viewed by 4762
Abstract
A decade of research on gluten-related disorders (GRDs) is reviewed in this study, with a particular emphasis on celiac disease (CD) and non-celiac gluten sensitivity (NCGS). GRDs are triggered by the ingestion of gluten and gluten-like proteins found in wheat, barley, and rye. [...] Read more.
A decade of research on gluten-related disorders (GRDs) is reviewed in this study, with a particular emphasis on celiac disease (CD) and non-celiac gluten sensitivity (NCGS). GRDs are triggered by the ingestion of gluten and gluten-like proteins found in wheat, barley, and rye. These proteins lead to intestinal damage in celiac disease, an autoimmune condition characterized by villous atrophy and a variety of gastrointestinal and extraintestinal symptoms. More enigmatic and less understood, NCGS involves symptoms similar to CD but without the immunological reaction or intestinal damage. Recent years have seen advances in the understanding of GRDs, particularly in connection to how intestinal microbiota influences disease progression and patient outcomes. The gluten-free diet (GFD) is still the standard therapy recommended for GRDs despite significant challenges, as discussed in this article. Precise diagnostic methods, patient education and dietary counseling are critical for improving patients’ quality of life. The purpose of this review is to provide a more clear and up-to-date understanding of GRDs, and to help further research on this important topic. Full article
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17 pages, 1053 KiB  
Review
Nutritional Consequences of Celiac Disease and Gluten-Free Diet
by Paola Ilaria Bianchi, Nicola Aronico, Giovanni Santacroce, Giacomo Broglio, Marco Vincenzo Lenti and Antonio Di Sabatino
Gastroenterol. Insights 2024, 15(4), 878-894; https://doi.org/10.3390/gastroent15040061 - 27 Sep 2024
Cited by 5 | Viewed by 8736
Abstract
Celiac disease is an immune-mediated condition triggered by gluten ingestion in genetically predisposed individuals. The global prevalence of celiac disease is significant, affecting approximately 1.4% of women and 0.7% of men, with incidence rates of 17.4 and 7.8 per 100,000 person-years, respectively. The [...] Read more.
Celiac disease is an immune-mediated condition triggered by gluten ingestion in genetically predisposed individuals. The global prevalence of celiac disease is significant, affecting approximately 1.4% of women and 0.7% of men, with incidence rates of 17.4 and 7.8 per 100,000 person-years, respectively. The clinical presentation of celiac disease may range from overt diarrhea and malabsorption to more subtle features such as nutritional deficiencies and extraintestinal manifestations. It is the most common cause of global malabsorption in Western countries. A life-long gluten-free diet is the only available treatment for celiac disease. Moreover, a gluten-free diet is often adopted by individuals without celiac disease, either to address non-celiac gluten sensitivity or for other reasons. This review aims to explore the current understandings of the nutritional consequences of untreated celiac disease and the impact of the gluten-free diet itself. Physicians and dietitians specializing in celiac disease should focus on providing a well-rounded nutritional scheme to address deficiencies caused by the disease and prevent the instauration of new nutritional imbalances. Full article
(This article belongs to the Special Issue Feature Papers in Celiac Disease)
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27 pages, 14394 KiB  
Article
Celiac Disease Deep Learning Image Classification Using Convolutional Neural Networks
by Joaquim Carreras
J. Imaging 2024, 10(8), 200; https://doi.org/10.3390/jimaging10080200 - 16 Aug 2024
Cited by 7 | Viewed by 2985
Abstract
Celiac disease (CD) is a gluten-sensitive immune-mediated enteropathy. This proof-of-concept study used a convolutional neural network (CNN) to classify hematoxylin and eosin (H&E) CD histological images, normal small intestine control, and non-specified duodenal inflammation (7294, 11,642, and 5966 images, respectively). The trained network [...] Read more.
Celiac disease (CD) is a gluten-sensitive immune-mediated enteropathy. This proof-of-concept study used a convolutional neural network (CNN) to classify hematoxylin and eosin (H&E) CD histological images, normal small intestine control, and non-specified duodenal inflammation (7294, 11,642, and 5966 images, respectively). The trained network classified CD with high performance (accuracy 99.7%, precision 99.6%, recall 99.3%, F1-score 99.5%, and specificity 99.8%). Interestingly, when the same network (already trained for the 3 class images), analyzed duodenal adenocarcinoma (3723 images), the new images were classified as duodenal inflammation in 63.65%, small intestine control in 34.73%, and CD in 1.61% of the cases; and when the network was retrained using the 4 histological subtypes, the performance was above 99% for CD and 97% for adenocarcinoma. Finally, the model added 13,043 images of Crohn’s disease to include other inflammatory bowel diseases; a comparison between different CNN architectures was performed, and the gradient-weighted class activation mapping (Grad-CAM) technique was used to understand why the deep learning network made its classification decisions. In conclusion, the CNN-based deep neural system classified 5 diagnoses with high performance. Narrow artificial intelligence (AI) is designed to perform tasks that typically require human intelligence, but it operates within limited constraints and is task-specific. Full article
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17 pages, 3273 KiB  
Article
γδ+ T-Cells Is a Useful Biomarker for the Differential Diagnosis between Celiac Disease and Non-Celiac Gluten Sensitivity in Patients under Gluten Free Diet
by Albert Martín-Cardona, Anna Carrasco, Beatriz Arau, Judith Vidal, Eva Tristán, Carme Ferrer, Gerardo Gonzalez-Puglia, Natàlia Pallarès, Cristian Tebé, Sergio Farrais, Concepción Núñez, Fernando Fernández-Bañares and Maria Esteve
Nutrients 2024, 16(14), 2294; https://doi.org/10.3390/nu16142294 - 17 Jul 2024
Cited by 5 | Viewed by 3983
Abstract
Background: The differential diagnosis between patients with celiac disease (CD) and non-celiac gluten sensitivity (NCGS) is difficult when a gluten-free diet (GFD) has been initiated before the diagnostic work-up. Isolated increases in TCRγδ+ and celiac lymphogram (increased TCRγδ+ plus decreased CD3−) may enable [...] Read more.
Background: The differential diagnosis between patients with celiac disease (CD) and non-celiac gluten sensitivity (NCGS) is difficult when a gluten-free diet (GFD) has been initiated before the diagnostic work-up. Isolated increases in TCRγδ+ and celiac lymphogram (increased TCRγδ+ plus decreased CD3−) may enable differential diagnosis in this challenging clinical setting. This study evaluated: (1) the accuracy of %TCRγδ+ and celiac lymphogram for diagnosing CD before and after GFD and for differentiation with NCGS; (2) TCRγδ+ kinetics at baseline and after starting GFD in both CD and NCGS. Methods: The inclusion criteria were patients with CD (n = 104), NCGS (n = 37), and healthy volunteers (n = 18). An intestinal biopsy for intraepithelial lymphogram by flow cytometry was performed at baseline and after GFD. The optimal cutoff for CD diagnostic accuracy was established by maximizing the Youden index and via logistic regression. Results: %TCRγδ+ showed better diagnostic accuracy than celiac lymphogram for identifying CD before and after GFD initiation. With a cutoff > 13.31, the accuracy for diagnosing CD in patients under GFD was 0.88 [0.80–0.93], whereas the accuracy for diagnosing NCGS (%TCRγδ+ ≤ 13.31) was 0.84 [0.76–0.89]. The percentage of TCRγδ+ cells showed differential kinetics between CD (baseline 22.7% [IQR, 16.4–33.6] vs. after GFD 26.4% [IQR, 17.8–36.8]; p = 0.026) and NCGS (baseline 9.4% [IQR, 4.1–14.6] vs. after GFD 6.4% [IQR, 3.2–11]; p = 0.022). Conclusion: TCRγδ+ T cell assessment accurately diagnoses CD before and after a GFD. Increased TCRγδ+ was maintained in the long term after GFD in CD but not in NCGS. Altogether, this suggests the potential usefulness of this marker for the differential diagnosis of these two entities in patients on a GFD. Full article
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10 pages, 466 KiB  
Article
Association of LPP and ZMIZ1 Gene Polymorphism with Celiac Disease in Subjects from Punjab, Pakistan
by Sumaira Zulfiqar, Amna Fiaz, Waqas Ahmed Khan, Misbah Hussain, Ansar Ali, Nadeem Ahmed, Basharat Ali and Muhammad Adnan Masood
Genes 2024, 15(7), 852; https://doi.org/10.3390/genes15070852 - 27 Jun 2024
Cited by 2 | Viewed by 1693
Abstract
Celiac disease (CD) is a complicated autoimmune disease that is caused by gluten sensitivity. It was commonly believed that CD only affected white Europeans, but recent findings show that it is also prevailing in some other racial groups, like South Asians, Caucasians, Africans, [...] Read more.
Celiac disease (CD) is a complicated autoimmune disease that is caused by gluten sensitivity. It was commonly believed that CD only affected white Europeans, but recent findings show that it is also prevailing in some other racial groups, like South Asians, Caucasians, Africans, and Arabs. Genetics plays a profound role in increasing the risk of developing CD. Genetic Variations in non-HLA genes such as LPP, ZMIZ1, CCR3, and many more influence the risk of CD in various populations. This study aimed to explore the association between LPP rs1464510 and ZMIZ1 rs1250552 and CD in the Punjabi Pakistani population. For this, a total of 70 human subjects were selected and divided into healthy controls and patients. Genotyping was performed using an in-house-developed tetra-amplification refractory mutation system polymerase chain reaction. Statistical analysis revealed a significant association between LPP rs1464510 (χ2 = 4.421, p = 0.035) and ZMIZ1 rs1250552 (χ2 = 3.867, p = 0.049) and CD. Multinomial regression analysis showed that LPP rs1464510 A allele reduces the risk of CD by ~52% (OR 0.48, CI: 0.24–0.96, 0.037), while C allele-carrying subjects are at ~2.6 fold increased risk of CD (OR 3.65, CI: 1.25–10.63, 0.017). Similarly, the ZMIZ1 rs1250552 AG genotype significantly reduces the risk of CD by 73% (OR 0.26, CI: 0.077–0.867, p = 0.028). In summary, Genetic Variations in the LPP and ZMIZ1 genes influence the risk of CD in Punjabi Pakistani subjects. LPP rs1464510 A allele and ZMIZ1 AG genotype play a protective role and reduce the risk of CD. Full article
(This article belongs to the Section Human Genomics and Genetic Diseases)
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