Non-coeliac gluten sensitivity

Abstract

Non-coeliac gluten sensitivity (NCGS) refers to individuals who report intestinal and extraintestinal symptoms related to the ingestion of gluten-based or wheat-based foods, in the absence of coeliac disease or wheat allergy. Gluten is found in multiple cereals, including wheat, rye, and barley, although the precise trigger of symptoms in NCGS remains unclear. Although approximately 10% of adults worldwide self-report gluten or wheat sensitivity, meta-analyses suggest that, during controlled challenge studies, 16-30% of these individuals have symptoms specifically triggered by gluten. However, methodological variability-including the presence of fermentable carbohydrates in challenge preparations-limits interpretation. Current evidence suggests that fermentable carbohydrates and nocebo effects contribute considerably to symptom generation in many cases. The substantial size of the gluten-free market raises questions about commercial and media influences on how NCGS is portrayed, and on the direction of related research. Definitive diagnosis of NCGS remains elusive due to the absence of biomarkers, significant overlap with disorders of gut-brain interaction, and methodological challenges in dietary evaluation. Until causative agents are identified and diagnostic tests developed, NCGS remains a diagnosis of exclusion, requiring careful systematic evaluation. Management approaches should balance dietary modification with recognition of psychological factors while ensuring nutritional adequacy. This Review critically examines current evidence regarding NCGS as a distinct entity, explores potential mechanisms, and provides practical guidance for assessment and management, while acknowledging major uncertainties in the field.