Non-celiac gluten sensitivity in depth

Non-celiac gluten sensitivity is a syndrome that is distinct from celiac disease and wheat allergy. Though the pathogenesis of non-celiac gluten sensitivity is poorly understood, gluten intake seems to be the major driver for the gastrointestinal, neurological and psychiatric symptoms experienced by people with non-celiac gluten sensitivity. There are significant symptomatic overlaps in patients suffering from celiac disease and non-celiac gluten sensitivity. 

An in-depth perspective on non-celiac gluten sensitivity

Non-celiac gluten sensitivity is a syndrome characterized by intestinal and extra-intestinal symptoms related to the ingestion of gluten-containing food, in subjects that are not diagnosed for celiac disease or wheat allergy [1, 2]. The prevalence of non-celiac gluten sensitivity is not clearly defined yet, however the prevalence has been estimated to be as high as 6 % of the general population, depending on the population studied [2]. In the United Stated and the United Kingdom, more than 10 % of adults currently started treatment with a gluten-free diet for different reasons and duration of time; however, many of these cases are self-diagnosed and not verified by a professional [3, 4].

In non-celiac gluten sensitivity clinical symptoms reach from intestinal disturbances (abdominal pain, diarrhea, nausea, body mass loss, bloating, and flatulence) to cutaneous (erythema, eczema), general systemic manifestations (e.g. “foggy mind”, headache, fatigue, bone and joint pain), anemia, behavioral (disturbance in attention, depression, and hyperactivity), and chronic ulcerative stomatitis [5, 6]. In contrast to celiac disease no specific genetic predisposition factor for non-celiac gluten sensitivity has been identified so far and serological biomarkers are not available for non-celiac gluten sensitivity, since the determination of celiac-related antibodies is not sensitive or specific to non-celiac gluten sensitivity [5, 6].

In contrast to celiac disease where the adaptive immune system is activated it seems that in non-celiac gluten sensitivity responses from the innate immune system are upregulated. In non-celiac gluten sensitivity no expression of genes involved in adaptive immune responses e.g. IL-6, IL-21 or IFNγ are activated. Rather, the patients’ gastrointestinal permeability is normal and lesions in the histological picture are minor [7, 8], but it has been observed that there exists an increased infiltration of eosinophils and basophils to the duodenal lamina propria and an activation of circulating basophils in non-celiac gluten sensitive patients [9, 10].

In recent years, several studies explored the relationship between the ingestion of gluten-containing food and the appearance of neurological and psychiatric disorders/symptoms like ataxia, peripheral neuropathy, schizophrenia, autism, depression, anxiety, and hallucinations (so-called gluten psychosis) and it has been suggested that gluten-related peptides can enter the systemic circulation and cause extraintestinal manifestations [5, 11].

Currently, non-celiac gluten sensitivity cannot be diagnosed without exclusion of wheat allergy and celiac disease. After exclusion of wheat allergy and celiac disease a food provocation test is applied. In contrast to wheat allergy symptoms, where IgE appears within 2 h after food intake, the adverse symptoms of non-celiac gluten sensitivity appear several hours or days after gluten consumption. An autoantibody, which is present in some non-celiac gluten sensitivity patients, is an IgG anti-gliadin antibody (IgG-AGA), which is also seen in celiac disease patients and negative IgG-AGA is related to good clinical response to a gluten-free diet [6].

Non-celiac gluten sensitivity is often described as an irritable bowl syndrome (IBS)-like entity due to the functional nature of the syndromes [12]. Furthermore, patients with self-reported non-celiac gluten sensitivity and IBS benefit from a dietary reduction of fermentable, oligo-, di-, monosaccharides, and polyols (FODMAPs) [13]. The efficacy of a low-FODMAPs diet in non-celiac gluten sensitivity and IBS patients suggest that some non-gluten components of wheat such as fructans, lectins, agglutinis and amylase-trypsin inhibitors may also trigger disease symptoms [14-17].



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