Non-celiac gluten sensitivity: questions still to be answered despite increasing awareness.

Abstract

"Recently, the increasing number of patients worldwide who are sensitive to dietary gluten without evidence of celiac disease or wheat allergy has contributed to the identification of a new gluten-related syndrome defined as non-celiac gluten sensitivity. Our knowledge regarding this syndrome is still lacking, and many aspects of this syndrome remain unknown. Its pathogenesis is heterogeneous, with a recognized pivotal role for innate immunity; many other factors also contribute, including low-grade intestinal inflammation, increased intestinal barrier function and changes in the intestinal microbiota. Gluten and other wheat proteins, such as amylase trypsin inhibitors, are the primary triggers of this syndrome, but it has also been hypothesized that a diet rich in fermentable monosaccharides and polyols may elicit its functional gastrointestinal symptoms. The epidemiology of this condition is far from established; its prevalence in the general population is highly variable, ranging from 0.63% to 6%. From a clinical point of view, non-celiac gluten sensitivity is characterized by a wide array of gastrointestinal and extraintestinal symptoms that occur shortly after the ingestion of gluten and improve or disappear when glutenis withdrawn from the diet. These symptoms recur when gluten is reintroduced. Because diagnostic biomarkers have not yet been identified, a double-blind placebo-controlled gluten challenge is currently the diagnostic method with the highest accuracy. Future research is needed to generate more knowledge regarding non-celiac glutensensitivity, a condition that has global acceptance but has only a few certainties and many unresolved issues."

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Non-celiac gluten sensitivity: the new frontier of gluten related disorders.

Abstract

"Non Celiac Gluten sensitivity (NCGS) was originally described in the 1980s and recently a "re-discovered" disorder characterized by intestinal and extra-intestinal symptoms related to the ingestion of gluten-containing food, in subjects that are not affected with either celiac disease (CD) or wheat allergy (WA). Although NCGS frequency is still unclear, epidemiological data have been generated that can help establishing the magnitude of the problem. Clinical studies further defined the identity of NCGS and its implications in human disease. An overlap between the irritable bowel syndrome (IBS) and NCGS has been detected, requiring even more stringent diagnostic criteria. Several studies suggested a relationship between NCGS and neuropsychiatric disorders, particularly autism and schizophrenia. The first case reports of NCGS in children have been described. Lack of biomarkers is still a major limitation of clinical studies, making it difficult to differentiate NCGS from other gluten related disorders. Recent studies raised the possibility that, beside gluten, wheat amylase-trypsin inhibitors and low-fermentable, poorly-absorbed, short-chain carbohydrates can contribute to symptoms (at least those related to IBS) experienced by NCGS patients. In this paper we report the major advances and current trends on NCGS."

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Does gluten cause gastrointestinal symptoms in subjects without coeliac disease?

Abstract

"AIM:

To determine the evidence for the effect of gluten ingestion on gastrointestinal symptoms, intestinal permeability and other indices of small intestinal injury in non-coeliac, gluten intolerant individuals.

METHODS:

A literature review was performed searching for interventional studies that addressed the issue.

RESULTS:

One unblinded study that identified symptomatic response to gluten did not effectively exclude patients with coeliac disease, since many had intraepithelial lymphocytosis. A double-blinded, randomised, placebo-controlled rechallenge trial was recently reported in patients in whom coeliac disease had been excluded by either normal duodenal histology on a gluten containing diet, or absence of the HLA DQ2 or DQ8 haplotype (56%). Participants were randomly assigned to receive either 16 g/day carbohydrate-free gluten or placebo for six weeks. Participants were enrolled if they had gastrointestinal symptoms that had improved on a GFD and had been on a gluten free diet for at least 6 weeks prior to enrollment. 19 received gluten and 15 received placebo. Change between baseline and final weeks were greater for patients receiving gluten in overall symptom severity compared with those receiving placebo (p=0.047). and were worse with gluten within one week for pain (p=0.016), bloating (p=0.031), satisfaction with stool consistency (p=0.024), and tiredness (p=0.001). Mechanisms for symptom induction were not identified.

CONCLUSIONS:

Non-coeliac gluten intolerance does exist. Future studies need to identify issues of the dose of gluten needed and mechanisms of action."

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Gluten causes gastrointestinal symptoms in subjects without celiac disease: a double-blind randomized placebo-controlled trial.

Abstract

"OBJECTIVES:

Despite increased prescription of a gluten-free diet for gastrointestinal symptoms in individuals who do not have celiac disease, there is minimal evidence that suggests that gluten is a trigger. The aims of this study were to determine whether gluten ingestion can induce symptoms in non-celiac individuals and to examine the mechanism.

METHODS:

A double-blind, randomized, placebo-controlled rechallenge trial was undertaken in patients with irritable bowel syndrome in whom celiacdisease was excluded and who were symptomatically controlled on a gluten-free diet. Participants received either gluten or placebo in the form of two bread slices plus one muffin per day with a gluten-free diet for up to 6 weeks. Symptoms were evaluated using a visual analog scale and markers of intestinal inflammation, injury, and immune activation were monitored.

RESULTS:

A total of 34 patients (aged 29-59 years, 4 men) completed the study as per protocol. Overall, 56% had human leukocyte antigen (HLA)-DQ2 and/or HLA-DQ8. Adherence to diet and supplements was very high. Of 19 patients (68%) in the gluten group, 13 reported that symptoms were not adequately controlled compared with 6 of 15 (40%) on placebo (P=0.0001; generalized estimating equation). On a visual analog scale, patients were significantly worse with gluten within 1 week for overall symptoms (P=0.047), pain (P=0.016), bloating (P=0.031), satisfaction with stool consistency (P=0.024), and tiredness (P=0.001). Anti-gliadin antibodies were not induced. There were no significant changes in fecal lactoferrin, levels of celiac antibodies, highly sensitive C-reactive protein, or intestinal permeability. There were no differences in any end point in individuals with or without DQ2/DQ8.

CONCLUSIONS:

"Non-celiac gluten intolerance" may exist, but no clues to the mechanism were elucidated."

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