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

Konstantinos Efthymakis,Michele Marchioni,Michele Sallese,Emanuela Clemente,Marta Di Nicola,Matteo Neri

doi:10.3390/ijms21061969

Konstantinos Efthymakis, Michele Marchioni + Show 4 more

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https://doi.org/10.3390/ijms21061969

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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.

Highlights

Non-celiac gluten/wheat sensitivity (NCGS/Non-celiac wheat sensitivity (NCWS)) is a syndrome dependent on gluten/wheat ingestion that presents both intestinal and extra-intestinal symptoms [1,2,3,4]
Total RNA isolated from the duodenal biopsies of 7 controls and 12 NCWS patients (Table 1) was used to assess gene expression by microarray analysis
NCWS diagnosis relies on the association of gluten ingestion with symptom severity in individuals where celiac disease has been excluded by the absence of serological markers [6]

Summary

Introduction

Non-celiac gluten/wheat sensitivity (NCGS/NCWS) is a syndrome dependent on gluten/wheat ingestion that presents both intestinal and extra-intestinal symptoms [1,2,3,4]. A more complete spectrum of NCWS clinical signs includes alternate bowel habits, bloating, abdominal pain, fatigue, foggy mind, limb numbness, dermatitis, and joint and muscle pain These symptoms largely overlap with those of other wheat-related disorders, including celiac disease and wheat allergy [3], as well as common intestinal disorders such as irritable bowel syndrome (IBS) [5]. Initially proposed as open-label [3], a more recent protocol, known as the Salerno criteria 6, entails the administration of a questionnaire where patients have to choose at least one and up to three main symptoms and give a score (ranging from 1 to 10) to their intensities during a short double-blind placebo-controlled gluten challenge. This gluten-centred diagnostic protocol does not take into account other wheat components (e.g., fermentable oligo-, di-, and monosaccharides (FODMAPs) and amylase trypsin inhibitor (ATI)) that may be important in NCWS [1,2,8]

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