Non-celiac Gluten Sensitivity: A New Clinical Entity or Growing Controversy?

Aims and background: Non-celiac gluten sensitivity (NCGS) has become an increasingly recognized condition, yet its diagnostic framework remains vague. Unlike celiac disease, NCGS lacks specific biomarkers and relies heavily on self-reported symptoms. Despite this ambiguity, the gluten-free product market reached USD 20.1 billion in 2021 and is projected to exceed USD 26.5 billion by 2030, indicating widespread adoption beyond medically justified use. Results: Emerging evidence suggests that gluten may not be the sole trigger in NCGS. Other wheat components, including amylase-trypsin inhibitors (ATIs), wheat germ agglutinin (WGA), and fructans, may contribute to symptom generation. Accordingly, the term "non-celiac wheat sensitivity (NCWS)" is increasingly preferred. Studies also show that low-FODMAP diets can alleviate symptoms attributed to NCGS, complicating the diagnostic distinction from irritable bowel syndrome (IBS) and other disorders of gut-brain interaction (DGBIs). The presence of antigliadin antibodies (AGA) or HLA-DQ2/DQ8 haplotypes may suggest predisposition, but these are neither specific nor diagnostic for NCGS. Conclusion: The lack of standardized diagnostic criteria and the influence of the nocebo effect pose significant challenges in the clinical assessment of NCGS. Self-reported outcomes alone are insufficient for a reliable diagnosis. Clinical significance: The unwarranted adoption of gluten-free diets in individuals without confirmed gluten-related disorders may lead to nutritional imbalance and disruption of the gut microbiota. Until validated diagnostic tools are established, clinicians should evaluate suspected NCGS cautiously, considering differential diagnoses and evidence-based dietary guidance. How to cite this article: Bektaş A. Non-celiac Gluten Sensitivity: A New Clinical Entity or Growing Controversy? Euroasian J Hepato-Gastroenterol 2025;15(2):170-172.