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Gluten/Wheat-Related Disorders: The Role of Nutrition, Gut Barrier, Microbiota, and New Therapeutic Strategies

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: 20 September 2026 | Viewed by 10014

Editor

Dr. Lisa Lungaro

E-Mail Website
Guest Editor
1. Arcispedale Sant'Anna, Azienda Ospedaliero-Universitaria di Ferrara Via Aldo Moro, 8 Cona, 44124 Ferrara, Italy
2. Policlinico Paolo Giaccone, Via del Vespro 129, 90127 Palermo, Italy
Interests: nutrition; celiac disease; gluten- related disorders; probiotics
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Gluten-related disorders (GRDs) include distinct conditions, specifically celiac disease (CD), wheat allergy (WA), and non-celiac gluten/wheat sensitivity (NCGWS).

The gut microbiome plays a vital role in immune regulation, and alterations in its composition may be associated with GRDs, including CD. Certain bacteria might enhance immune responses by mimicking gliadin or exacerbating intestinal inflammation with gluten. The microbiome also affects the development of antigens, intestinal permeability, and the production of pro-inflammatory or anti-inflammatory cytokines. Genetic predispositions and early life experiences significantly shape the initial gut microbiome.

Disruptions in the epithelial barrier have also been observed across all three of these clinical conditions. However, its potential role as a pathogenetic co-factor—especially in CD and NCGWS—remains under investigation.

Currently, the sole effective treatment for CD is a stringent GFD. However, some patients continue to experience symptoms and exhibit partial villus atrophy due to gluten exposure, indicating that the GFD may not fully manage symptoms. Emerging therapeutic strategies being explored include gluten proteolysis, removal of gluten from the digestive system, promotion of tight junction integrity, inhibition of transglutaminase 2, utilization of probiotics, and immunotherapy.

This Special Issue of IJMS aims to showcase the latest developments in GFD for CD and other GRDs from a comprehensive viewpoint. It covers areas such as diet and nutrition, innovative techniques for gluten analysis, evaluation of gut barrier integrity, case reports featuring molecular-level data analysis, and complementary or alternative treatments, such as gluten-free wheat flours, probiotics, and medications.

Dr. Lisa Lungaro
Guest Editor

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Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-anonymized peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • gluten-related disorders
  • celiac disease
  • non celiac gluten wheat sensitivity
  • gluten free diet
  • microbiota
  • gut barrier
  • probiotics

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Published Papers (2 papers)

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27 pages, 556 KB  
Review
Non-Coeliac Wheat Sensitivity: Symptoms in Search of a Mechanism, or a Distinct Well-Defined Clinical Entity? A Narrative Review
by Stiliano Maimaris, Chiara Scarcella, Giusi Aurora Memoli, Carlotta Crisciotti, Annalisa Schiepatti and Federico Biagi
Int. J. Mol. Sci. 2025, 26(22), 11174; https://doi.org/10.3390/ijms262211174 - 19 Nov 2025
Viewed by 7327
Abstract
Non-coeliac wheat sensitivity (NCWS) is characterised by gastrointestinal and extra-intestinal symptoms following gluten/wheat ingestion in individuals without coeliac disease or wheat allergy but remains controversial due to symptom overlap with irritable bowel syndrome (IBS). This narrative review aims to provide a comprehensive, critical [...] Read more.
Non-coeliac wheat sensitivity (NCWS) is characterised by gastrointestinal and extra-intestinal symptoms following gluten/wheat ingestion in individuals without coeliac disease or wheat allergy but remains controversial due to symptom overlap with irritable bowel syndrome (IBS). This narrative review aims to provide a comprehensive, critical analysis of NCWS as a clinical and biological entity, examining the evidence for its distinction from related disorders. While self-reported rates are high (often >10%) in the general population, rigorous double-blind, placebo-controlled challenge (DBPCC) studies confirm the diagnosis in only a minority of cases (typically <30%). The clinical presentation is heterogeneous, combining IBS-like symptoms with systemic complaints such as “brain fog,” headaches, and fatigue. The pathophysiology is distinct from coeliac disease, involving innate immune activation, altered intestinal barrier function, and gut dysbiosis. Non-gluten wheat components, particularly fructans and amylase-trypsin inhibitors, are implicated as potential triggers. Diagnosis is challenging, requiring the exclusion of other disorders and adherence to complex dietary challenge protocols such as the Salerno Experts’ Criteria, which are impractical for routine clinical use. The search for validated biomarkers is a key research area and investigated candidates include serological markers such as IgG anti-gliadin antibodies, inflammatory markers such as faecal calprotectin, and proteins related to intestinal permeability such as zonulin, but results have been conflicting and require further validation. Management primarily involves elimination of wheat and gluten from the diet, although a low-FODMAP diet has also proven effective as an adjunctive treatment. In conclusion, NCWS is a clinical entity whose study and management are critically hampered by the absence of validated diagnostic criteria and biomarkers. Progress requires methodologically rigorous DBPCC trials to elucidate its mechanisms and develop reliable diagnostic tools. Full article
(This article belongs to the Special Issue Gluten/Wheat-Related Disorders: The Role of Nutrition, Gut Barrier, Microbiota, and New Therapeutic Strategies)
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9 pages, 350 KB  
Brief Report
Uncovering Hidden Gluten Exposure in Celiac Patients: A Case Study in Family-Based Management and the Role of Point-of-Care Urine Testing and Psychological Assessment
by Ángela Ruiz-Carnicer, Cristóbal Coronel-Rodríguez, María Cinta Guisado-Rasco, Isabel Comino, Carolina Sousa and Verónica Segura
Int. J. Mol. Sci. 2025, 26(11), 5135; https://doi.org/10.3390/ijms26115135 - 27 May 2025
Cited by 2 | Viewed by 2057
Abstract
Celiac disease (CD) is a chronic immune-mediated enteropathy that requires strict adherence to a gluten-free diet (GFD) to prevent intestinal damage. Traditional methods for monitoring GFD adherence, such as serology and dietary assessments, often poorly correlate with histological findings and typically involve a [...] Read more.
Celiac disease (CD) is a chronic immune-mediated enteropathy that requires strict adherence to a gluten-free diet (GFD) to prevent intestinal damage. Traditional methods for monitoring GFD adherence, such as serology and dietary assessments, often poorly correlate with histological findings and typically involve a waiting period before results are available, limiting their usefulness for immediate clinical decision-making. This cross-sectional case study reports on a 45-year-old mother and her 11-year-old twin daughters, all diagnosed with CD and following a GFD for over two years. Despite being asymptomatic and showing negative anti-tTG serology, the mother continued to present Marsh 1 histological lesions, suggesting ongoing subclinical inflammation. Point-of-care testing (POCT) for gluten immunogenic peptides (GIP) in urine revealed positive results for all three individuals, indicating recent gluten exposure despite reported dietary adherence. A follow-up GIP test after dietary review and reinforcement yielded negative results, confirming improved adherence. Additionally, a psychological assessment using the Hospital Anxiety and Depression Scale (HADS) revealed anxiety symptoms in the mother and one of the daughters, which may have influenced adherence to the GFD. These findings underscore the clinical value of urinary GIP POCT as a rapid, non-invasive tool for detecting hidden gluten exposure, even when traditional monitoring appears normal. Integrating GIP testing and psychological screening into routine clinical practice may enhance management and support timely, personalized interventions in patients with CD. Full article
(This article belongs to the Special Issue Gluten/Wheat-Related Disorders: The Role of Nutrition, Gut Barrier, Microbiota, and New Therapeutic Strategies)
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