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Nutritional and Clinical Approaches Across the Spectrum of Gluten-Related Disorders

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Dear Colleagues,

Gluten-related disorders, including celiac disease, non-celiac gluten sensitivity and wheat allergy, comprise a heterogeneous spectrum with distinct mechanisms, clinical phenotypes and nutritional challenges that require responses beyond the traditional gluten-free diet (GFD) paradigm. Despite widespread GFD prescription, many patients present persistent micronutrient deficiencies, suboptimal dietary patterns, altered body composition, ongoing symptoms and gut microbiota alterations, highlighting the need for more precise and clinically structured approaches.

This Special Issue aims to provide a focused and innovative platform for studies that clarify how nutritional assessment and targeted interventions can be tailored across gluten-related disorders, emphasizing mechanisms, clinically actionable biomarkers and patient-centered outcomes. We particularly welcome original research and high-quality reviews that: (i) apply advanced tools (e.g., omics-based profiling, microbiome analyses, body composition techniques and digital dietary assessment) to refine risk stratification and follow-up; (ii) explore the interplay between nutritional status, immune and metabolic responses and symptom burden; and (iii) develop or test structured, evidence-based algorithms for monitoring and optimizing nutritional and clinical care. By prioritizing mechanistically informed and clinically translatable work, this Special Issue seeks to move beyond generic or incremental contributions to offer a distinct, up-to-date framework for improving long-term health and quality of life in individuals with gluten-related disorders.

Prof. Dr. Maria Teresa Nestares Pleguezuelo
Dr. Lara Bossini-Castillo
Guest Editors

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14 pages, 768 KB

Open AccessArticle

Clinical Utility of Anti-Gliadin IgG Antibody (AGA IgG) and Characterization of Patients with Suspected Non-Celiac Gluten Sensitivity: Prospective, Observational Study in Japan

by Mikuni Motoyama, Hisashi Yamada, Chiho Yoshimura and Hisato Matsunaga

Nutrients 2026, 18(10), 1607; https://doi.org/10.3390/nu18101607 - 18 May 2026

Viewed by 333

Abstract

Background/Objectives: Non-celiac gluten sensitivity (NCGS) is a syndrome characterized by intestinal and extraintestinal symptoms triggered by gluten ingestion. Although anti-gliadin IgG antibody (AGA IgG) has been proposed as a potential biomarker for NCGS, its sensitivity and specificity in real-world clinical settings remain unclear. This study aimed to evaluate the clinical utility of AGA IgG in NCGS and to characterize its clinical features, including psychological distress and physical quality of life (QOL), in patients with clinically suspected NCGS attending a specialized outpatient unit in Japan, where patients reported symptoms related to the ingestion of gluten-containing grains (primarily wheat). Methods: We evaluated plasma AGA IgG levels in 45 patients with suspected NCGS based on clinical presentation and in 83 age- and sex-matched healthy controls. Plasma AGA IgG was measured using ELISA. Clinical symptoms and QOL were assessed using validated scales, including the 36-Item Short Form Health Survey (SF-36), Patient Health Questionnaire (PHQ-9 and PHQ-15), Generalized Anxiety Disorder-7 (GAD-7), and the Japanese version of the Irritable Bowel Syndrome Quality of Life measure (IBS-QOL-J). Results: The AGA IgG positivity rate was significantly higher in the suspected NCGS group (33.3%) than in the control group (13.3%; p < 0.01). Using clinical suspicion as the reference, the sensitivity and specificity of AGA IgG were 33.3% and 86.7%, respectively. Patients with suspected NCGS exhibited significantly lower physical and mental QOL and higher scores for depressive, anxiety, and somatic symptoms compared to controls. No significant clinical differences were found between AGA IgG-positive and IgG-negative individuals within the suspected NCGS group. Conclusions: AGA IgG demonstrated a specificity of 86.7% and a sensitivity of 33.3% for suspected NCGS, indicating its limited utility as a standalone biomarker. These findings suggest that suspected NCGS involves significant somatic and psychological burdens regardless of serological status. Future studies should explore whether a multi-marker panel could improve the identification of “True NCGS” in diverse clinical populations. Full article

(This article belongs to the Special Issue Nutritional and Clinical Approaches Across the Spectrum of Gluten-Related Disorders)

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