Non-celiac wheat sensitivity: differential diagnosis, triggers and implications

Area of Science:

• Immunology
• Gastroenterology
• Nutrition Science

Background:

• Non-celiac wheat sensitivity (NCWS) is a debated diagnosis, often overlooked due to lack of clear inflammatory markers.
• Distinguishing NCWS from celiac disease and wheat allergy is crucial, with carbohydrate intolerances like FODMAPs also needing exclusion.
• Recent evidence suggests NCWS is a genuine condition with a significant prevalence.

Purpose of the Study:

• To investigate the immunological basis of NCWS.
• To identify the specific wheat components responsible for NCWS symptoms.
• To explore the role of NCWS in both gastrointestinal and extraintestinal conditions.

Main Methods:

• Review of recent studies and experimental data on NCWS.
• Analysis of the immunological mechanisms involving wheat components.
• Identification of potential triggers and their interaction with the immune system.

Main Results:

• Wheat amylase-trypsin inhibitors (ATIs) are identified as the likely triggers of NCWS.
• ATIs activate the toll-like receptor 4 (TLR4) complex in immune cells of the intestinal mucosa.
• Non-gluten cereals show minimal TLR4 stimulating activity compared to wheat ATIs.
• Wheat ATIs can promote T cell activation, impacting immune-mediated diseases.

Conclusions:

• NCWS is an innate immune response to wheat ATIs, not solely a gastrointestinal issue.
• ATIs are potent immune stimulators, contributing to symptoms in NCWS and potentially exacerbating other inflammatory diseases.
• Understanding ATIs' role is key for diagnosing and managing NCWS and related immune conditions.