Non-coeliac gluten sensitivity.

Irritable bowel syndrome-like symptoms in response to wheat ingestion is common and well described, but whether the reaction is due to gluten (i.e., non-coeliac gluten sensitivity), other wheat proteins, or FODMAPs (mostly fructans) alone or in combinations has not been clearly defined. Exclusion of coeliac disease in the presence of negative serology, and normal villous architecture but increased density of intraepithelial lymphocytes on duodenal biopsies, is difficult. Furthermore, the confidence by which a positive diagnosis is made or non-coeliac gluten sensitivity is excluded by blinded placebo-controlled rechallenge with wheat protein is reduced by strong nocebo responses generally found in patients with self-reported non-coeliac gluten sensitivity. The absence of a clear biological mechanism of action and difficulties with the design and interpretation of research studies have plunged this entity into even deeper controversy. In the absence of clarity in its diagnosis, the epidemiology, prognosis, and therapeutic approaches to a patient who may be gluten sensitive remain to be determined. Adequate understanding of the issues surrounding the controversy and further research will slowly unravel the truth behind the problem.