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

Abstract

Gluten-free diets are increasingly chosen in the Western world, even in the absence of a diagnosis of celiac disease. Around 10% of people worldwide self-report gluten-related complaints, including intestinal and extra-intestinal symptoms. In most cases, these subjects would be labeled as patients suffering from irritable bowel syndrome (IBS) who place themselves on a gluten-free diet even in the absence of celiac disease. In some instances, patients report a clear benefit by avoiding gluten from their diet and/or symptom worsening upon gluten reintroduction. This clinical entity has been termed non-celiac gluten sensitivity (NCGS). The symptoms referred by these patients are both intestinal and extra-intestinal, suggesting that similarly to functional gastrointestinal disorders, NCGS is a disorder of gut–brain interaction. It remains unclear if gluten is the only wheat component involved in NCGS. The mechanisms underlying symptom generation in NCGS remain to be fully clarified, although in the past few years, the research has significantly moved forward with new data linking NCGS to changes in gut motility, permeability and innate immunity. The diagnosis is largely based on the self-reported reaction to gluten by the patient, as there are no available biomarkers, and confirmatory double-blind challenge protocols are unfeasible in daily clinical practice. Some studies suggest that a small proportion of patients with IBS have an intolerance to gluten. However, the benefits of gluten-free or low-gluten diets in non-celiac disease-related conditions are limited, and the long-term consequences of this practice may include nutritional and gut microbiota unbalance. Here, we summarize the role of gluten in the clinical features, pathophysiology, and management of NCGS and disorders of gut–brain interaction.

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

“…Non-celiac gluten/wheat sensitivity (NCGS/WS) is a clinical entity characterized by intestinal and extraintestinal symptoms induced by gluten ingestion in the absence of wheat allergy (WA) or celiac disease (CD) [ 1 , 2 ]. Components of wheat other than gluten have also been suggested to contribute to NCGS/WS symptoms.…”

“…Components of wheat other than gluten have also been suggested to contribute to NCGS/WS symptoms. Specifically, there is supportive data from clinical trials for the potential involvement of fermentable oligo-, di-, monosaccharides, and polyols (FODMAPs) [ 1 , 2 ]. Several different substances other than gluten, such as fermentable oligo-, di-, monosaccharides, and polyols (FODMAPs), amylase trypsin inhibitors (ATIs), wheat germ agglutinin (WGA), and glyphosate may be involved in its pathogenesis [ 1 , 2 ].…”

“…Specifically, there is supportive data from clinical trials for the potential involvement of fermentable oligo-, di-, monosaccharides, and polyols (FODMAPs) [ 1 , 2 ]. Several different substances other than gluten, such as fermentable oligo-, di-, monosaccharides, and polyols (FODMAPs), amylase trypsin inhibitors (ATIs), wheat germ agglutinin (WGA), and glyphosate may be involved in its pathogenesis [ 1 , 2 ]. Gluten peptides are resistant to gastrointestinal proteolytic degradation and may elicit immunogenic responses, alter the intestinal permeability, and promote oxidative stress and pro-inflammatory and cytotoxic effects [ 1 , 2 ].…”

“…Several different substances other than gluten, such as fermentable oligo-, di-, monosaccharides, and polyols (FODMAPs), amylase trypsin inhibitors (ATIs), wheat germ agglutinin (WGA), and glyphosate may be involved in its pathogenesis [ 1 , 2 ]. Gluten peptides are resistant to gastrointestinal proteolytic degradation and may elicit immunogenic responses, alter the intestinal permeability, and promote oxidative stress and pro-inflammatory and cytotoxic effects [ 1 , 2 ]. Indeed, FODMAPs may act by osmotic activity, fluid retention, fermentation and gas production, and ATIs/WGA through immune responses, pro-inflammatory effects, and intestinal barrier disruption, respectively [ 1 , 2 ].…”

Histamine Intolerance Originates in the Gut

“…Currently, approximately 20% of the population are avoiding gluten in food because of a self-diagnosed, new clinical condition, referred to as non-celiac gluten sensitivity (NCGS). Unproven hypotheses of supposed health benefits due to gluten-free eating are wide-spread [ 51 ]. There are no medical tests available for the diagnosis of NCGS, and patients were also named “people without celiac disease avoiding gluten” [ 52 ].…”