Clinical utility of gluten restriction in gastrointestinal disorders: Evidence, practice, and reappraisal of non-coeliac gluten sensitivity

Best Pract Res Clin Gastroenterol. 2025 Dec:79:102086. doi: 10.1016/j.bpg.2025.102086. Epub 2025 Dec 15.

Abstract

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.

Keywords: Disorders of gut–brain interaction; FODMAPs; Gluten-free diet; Irritable bowel syndrome.

Publication types

  • Review

MeSH terms

  • Celiac Disease / diagnosis
  • Celiac Disease / diet therapy
  • Diet, Gluten-Free*
  • Gastrointestinal Diseases* / diagnosis
  • Gastrointestinal Diseases* / diet therapy
  • Gastrointestinal Diseases* / physiopathology
  • Glutens* / adverse effects
  • Humans

Substances

  • Glutens