Nonceliac Wheat Sensitivity: An Immune-Mediated Condition with Systemic Manifestations

Abstract

Non-celiac wheat sensitivity (NCWS) is characterized by gastrointestinal and extra-intestinal symptoms following the ingestion of gluten-containing cereals in subjects without celiac disease or wheat allergy. The identity of the molecular triggers in these cereals responsible for the symptoms of NCWS remains to be delineated. Recent research has identified a biological basis for the condition, with the observation of systemic immune activation in response to microbial translocation that appears to be linked to intestinal barrier defects. Ongoing research efforts are aimed at further characterizing the etiology, mechanism, and biomarkers of the condition.

Keywords: Amylase/protease inhibitor; Antibody to native gliadin; Biomarkers; Fructan; Gluten; Intestinal barrier function; Systemic immune activation; Wheat.

Figure 1:

Diagrammatic representation of the proposed sequence of events in non-celiac wheat sensitivity (NCWS) based on the available data.

Figure 2:

Suggested diagnostic algorithm for patients adhering to a gluten free diet (GFD) without having previously ruled out celiac disease.

Figure 3:

Different components of wheat, such as gluten, fructans (as part of fermentable oligo-, di-, and mono-saccharides, and polyols, FODMAPs), amylase-trypsin inhibitors (ATIs), and other molecules may act as triggers of non-celiac wheat sensitivity (NCWS), including immune system modulation, intestinal barrier disruption, and symptom generation.