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

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.

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.

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.

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.

Bektaş A. Non-celiac Gluten Sensitivity: A New Clinical Entity or Growing Controversy? Euroasian J Hepato-Gastroenterol 2025;15(2):170-172.