Gluten-free diets (GFDs) are widely adopted for gastrointestinal complaints, yet evidence from well-controlled gluten challenge studies supporting gluten-specific symptom generation outside coeliac disease is inconsistent. Across trials, reproducible gluten-specific effects largely disappear once fermentable carbohydrates (FODMAPs) and expectation biases are controlled for, and meta-analyses report only modest, inconsistent symptom relief. Large nocebo responses and methodological heterogeneity undermine confidence in the construct of “non-coeliac gluten sensitivity”. Re-interpreting gluten-attributed symptoms through the paradigm of disorders of gut–brain interaction provides a clinically coherent framework that integrates visceral hypersensitivity, cognitive-affective processes and sociocultural drivers. This review synthesises mechanistic and clinical data, distils methodological lessons and offers practical guidance on when, and how, to consider gluten restriction. A GFD should be a last resort, time-limited probe, supervised by a dietitian, and embedded within multidisciplinary care focused on individual symptom mechanisms.

Gluten-free diet

Irritable bowel syndrome

Disorders of gut–brain interaction

FODMAPs

© 2025 The Author. Published by Elsevier Ltd.