Abstract

Non-celiac gluten sensitivity (NCGS) is a clinical entity characterized by the absence of celiac disease and wheat allergy in patients that trigger reproducible symptomatic responses to gluten-containing foods consumption. Due to the lack of sensitive and reproducible biomarkers for NCGS diagnosis, placebo-controlled gluten challenges must be carried out for its diagnosis. The gluten challenges can be either double- or single-blind, for research or clinical practice purposes, respectively. For improving our understanding about the magnitude and relevance of NCGS in different populations, epidemiological studies based on self-report have been carried out. However, the gluten challenge-based prevalence of NCGS remains to be estimated. Since NCGS was recently recognized as a clinical entity, more studies are needed to delve into NCGS pathogenesis, for instance, the molecular interactions between the suspected cereal grain components that trigger NCGS, such as fermentable oligo-, di-, monosaccharides, and polyols (FODMAPs) and amylase and trypsin inhibitors, and the immune system remains to be elucidated. Although still under debate, NCGS patients can be susceptible to only one or more than one of the NCGS triggers. The treatment of NCGS involves the dietary restriction of the suspected triggers of the disease, but there is controversial data about the effectiveness of different dietary interventions such as the gluten-free diet and low-FODMAP diet. Certainly, our understanding of NCGS is improving quickly due to the constant availability of new scientific information on this topic. Thus, the aim of the present narrative review is to present an up-to-date overview on NCGS from epidemiology to current therapy.

Highlights

  • Some disorders may occur when consuming some specific wheat components, such as gliadins, glutenins, and fermentable oligo, di, monosaccharides, and polyols (FODMAPs). These disorders are known as gluten-related disorders (GRDs) and mainly involve celiac disease (CD), wheat allergy (WA), and non-celiac gluten sensitivity (NCGS) [4]

  • CD is an enteropathy with autoimmune characteristics and it is triggered by gluten-containing foods in susceptible individuals that carry human leukocyte antigen (HLA)-DQ2 and/or HLADQ8 haplotypes [5]

  • NCGS is characterized by the triggering of intestinal and/or extraintestinal symptoms after the consumption of products made with gluten-containing cereals, but both CD and WA must be properly ruled out as the symptoms overlap among the clinical entities and there is a lack of sensible and specific biomarkers for NCGS diagnosis [7]

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Summary

Introduction

Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. The triggering of wheat-induced symptoms in subjects that underwent double-blind placebo-controlled (DBPC) gluten challenges and in whom CD and WA were ruled out was reported until the beginning of the second decade of the 21st century [10,11]. These reports gave rise to intensive research to elucidate the underlying mechanisms of NCGS, identify the specific triggers of the disease and biomarkers for its diagnosis, and know the best treatment of NCGS and its epidemiology. The aim of this narrative review is to present an up-to-date overview on NCGS considering the fundamental factors of this clinical entity and covering different topics, from epidemiology to current therapy

Definition
Epidemiology
Clinical Picture
Current Knowledge on the Pathogenesis of NCGS
Diagnosis
Study Limitations
15 RNA transcripts
Dietary Treatment
Findings
Perspectives
Full Text
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