An Exploratory Gene Expression Study of the Intestinal Mucosa of Patients with Non-Celiac Wheat Sensitivity

Abstract

Non-celiac wheat sensitivity (NCWS) is a recently recognized syndrome triggered by a gluten-containing diet. The pathophysiological mechanisms engaged in NCWS are poorly understood and, in the absence of laboratory markers, the diagnosis relies only on a double-blind protocol of symptoms evaluation during a gluten challenge. We aimed to shed light on the molecular mechanisms governing this disorder and identify biomarkers helpful to the diagnosis. By a genome-wide transcriptomic analysis, we investigated gene expression profiles of the intestinal mucosa of 12 NCWS patients, as well as 7 controls. We identified 300 RNA transcripts whose expression differed between NCWS patients and controls. Only 37% of these transcripts were protein-coding RNA, whereas the remaining were non-coding RNA. Principal component analysis (PCA) and receiver operating characteristic curves showed that these microarray data are potentially useful to set apart NCWS from controls. Literature and network analyses indicated a possible implication/dysregulation of innate immune response, hedgehog pathway, and circadian rhythm in NCWS. This exploratory study indicates that NCWS can be genetically defined and gene expression profiling might be a suitable tool to support the diagnosis. The dysregulated genes suggest that NCWS may result from a deranged immune response. Furthermore, non-coding RNA might play an important role in the pathogenesis of NCWS.

Non-Celiac Gluten/Wheat Sensitivity: Clinical Characteristics and Microbiota and Mycobiota Composition by Response to the Gluten Challenge Test

“…The pathogenesis of NCGS/WS is still uncertain; a higher intestinal expression of toll-like receptors suggesting a stronger implication of the innate immune mechanisms, the infiltration of immune cells in the gut mucosa, increased expression of antibodies, and dysregulated gene expression profiling and epigenetic mechanisms have been described [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 ]. Furthermore, impaired intestinal barrier and permeability and gut dysbiosis have been advocated as key factors by several studies [ 1 , 2 , 4 , 10 , 11 ].…”

Non-Celiac Gluten Sensitivity in the Context of Functional Gastrointestinal Disorders

“…The protein-coding RNA differently expressed in the NCGS group was related to inflammation and immune response. Unfortunately, these data belong to a small number of patients; in addition, they were not validated in an external cohort, and NCGS patients were diagnosed according to an open gluten challenge [77]. For all these reasons, these preliminary results need to be confirmed in future studies.…”

Non-Celiac Gluten Sensitivity: An Update

“…Up-regulated levels of interleukin (IL) 10, transforming growth factor (TGF) α, C-X-C motif chemokine ligand 10 (CXCL-10), and granulocyte-macrophage colony-stimulating factor (GM-CSF), CD14, and lipopolysaccharide (LPS)-binding protein have also been reported in wheat-sensitive individuals in the absence of CD [ 46 , 47 , 48 ]. Furthermore, the expression of RNA transcripts that could be implicated in the activation of the innate immune system, such as zurocidin 1 (AZU1), bone morphogenetic protein-7 (BMP7), cluster of differentiation 70 (CD70), among others, have been documented in the intestinal mucosa of NCGS patients [ 49 ]. These data support the notion that there is a predominant role of the innate immune system in NCGS.…”