Effects of wheat germ agglutinin on human gastrointestinal epithelium: Insights from an experimental model of immune/epithelial cell interaction

Pellegrina, Chiara Dalla; Perbellini, Omar; Scupoli, Maria Teresa; Tomelleri, Carlo; Zanetti, Chiara; Zoccatelli, Gianni; Fusi, Marina; Peruffo, A. Dal Belin; Rizzi, Corrado; Chignola, Roberto

doi:10.1016/j.taap.2009.03.012

Cited by 67 publications

(49 citation statements)

References 35 publications

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“…Murine peritoneal macrophages responded with high proinflammatory cytokine secretion to WGA stimulation in vitro (TNF-α, IL-1β, IL-12, and IFN-γ) [30]. Similarly, stimulation of isolated human PBMC with minimal amounts of WGA elicited the release of proinflammatory cytokines [31]. These results indicate that WGA have a high potential to initiate or maintain inflammatory responses.…”

Section: Pathophysiology Of Ncgsmentioning

confidence: 99%

Non-Celiac Gluten Sensitivity: A Challenging Diagnosis in Children with Abdominal Pain

Ruemmele

2018

Ann Nutr Metab

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Several disorders related to the ingestion of gluten are well recognized despite overlapping clinical presentations: celiac disease, an autoimmune enteropathy triggered by gluten ingestions in susceptible individuals, allergy to wheat, and more recently non-celiac gluten sensitivity (NCGS). While celiac disease and wheat allergy are well-known disorders with a clear-cut diagnosis based on clinical tests and biological parameters, NCGS is a more difficult diagnosis, especially in children with functional gastrointestinal (GI) complaints. NCGS is considered a syndrome of intestinal but also extraintestinal symptoms occurring within hours, but sometimes even after several days of gluten ingestion. In children, the leading symptoms of NCGS are abdominal pain and diarrhea, while extraintestinal symptoms are rare, in contrast to adult patients. No precise diagnostic test nor specific biomarkers exist, except a rather cumbersome three-phase gluten-exposure, gluten-free diet, followed by a blinded placebo-controlled gluten challenge with crossover to provoke symptoms elicited by gluten in a reproducible manner that disappear on gluten-free alimentation. Recent data indicate that the peptide part of wheat proteins is not necessarily the sole trigger of clinical symptoms. Mono- or oligosaccharides, such as fructan and other constituents of wheat, were able to provoke GI symptoms in clinical trials. These new findings indicate that the term gluten sensitivity is probably too restrictive. The incidence of NCGS was reported in the range of 1–10% in the general population and to increase steadily; however, most data are based on patients’ self-reported gluten intolerance or avoidance without a medically confirmed diagnosis. Treatment consists of gluten avoidance for at least several weeks or months. Patients with NCGS require regular reassessment for gluten tolerance allowing with time the reintroduction of increasing amounts of gluten.

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Section: Pathophysiology Of Ncgsmentioning

confidence: 99%

Non-Celiac Gluten Sensitivity: A Challenging Diagnosis in Children with Abdominal Pain

Ruemmele

2018

Ann Nutr Metab

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“…Preliminary studies demonstrate that they can inhibit repair of gut epithelial cells and also stimulate the synthesis of proinflammatory cytokines leading to gastrointestinal symptoms. 95,96 Therefore, given the current uncertainties regarding which gluten-based constituent is triggering symptoms, it is of some investigators' opinion that patients (particularly those who are AGA negative) should be informed that owing to the absence of diagnostic biomarkers, their condition can be considered as "self-reported" NCGS or noncoeliac wheat sensitivity, or "patients who avoid wheat and/or gluten". 41,97 When available, DBPC rechallenges should use specifically isolated gluten-based constituents, and ideally present them in capsulated form to help prevent any potential ambiguity.…”

Section: Uncertainties and Future Directionsmentioning

confidence: 99%

The spectrum of noncoeliac gluten sensitivity

Aziz

Hadjivassiliou

Sanders

2015

Nat Rev Gastroenterol Hepatol

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The past 5 years have seen an increase in the use of a gluten-free diet outside a diagnosis of coeliac disease or IgE-mediated wheat allergy. This trend has led to the identification of a new clinical entity termed noncoeliac gluten sensitivity (NCGS). In this Review, we discuss the evidence for NCGS as demonstrated by the results of double-blind, placebo-controlled dietary rechallenge studies. Furthermore, the characteristic phenotype of individuals with NCGS is described as well as the symptom manifestations commonly reported after gluten exposure, which include intestinal symptoms consistent with IBS, and extraintestinal symptoms such as neurological dysfunction, psychological disturbances, fibromyalgia and skin rash. Moreover, emerging evidence suggests that NCGS can be associated with organic gastrointestinal pathologies, such as IBD, in which its presence might be a reflection of severe or stricturing disease. However, NCGS is not without its controversies and uncertainties, in particular pertaining to whether it is gluten or nongluten components of the grain evoking symptoms; evidence suggests that fermentable carbohydrates, amylase trypsin inhibitors and wheat-germ agglutinin can also be responsible culprits. Finally, we discuss the novel techniques that might help diagnose NCGS in the future.

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“…There are moderate to large amounts present in wheat germ, whole grains and some processed grains, and these are unlikely to be significantly degraded in the gastrointestinal tract. Only minute concentrations of the lectin are needed for its actions in epithelial models in vitro [28]. Thus, it would appear that WGA is a likely candidate to exert effects on epithelia and inflammatory cells in the human intestine, and this would be exaggerated if epithelial permeability was compromised.…”

Section: Components Of Wheatmentioning

confidence: 99%

Other Dietary Confounders: FODMAPS et al.

Gibson

Muir

Newnham

2015

Dig Dis

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Background: While it is well documented and widely appreciated that ingestion of wheat (and less so rye and barley) is associated with gastrointestinal symptoms such as bloating or abdominal pain, the component of wheat to which such an effect is attributed is less well established. Key Messages: Wheat is a complex of proteins (80% gluten, 20% metabolic proteins), carbohydrates (starch, non-starch polysaccharides, fructans), lipids and other components. The majority of attention has focused on gluten as the culprit in triggering symptoms, but re-challenge studies have nearly all used wheat flour-related products (such as bread) as the stimulus. When carbohydrate-deplete gluten was used as the challenge agent, gluten-specific feelings of depression and not gut symptoms were observed in those who fulfilled strict criteria of ‘non-coeliac gluten sensitivity', thereby underlining the complexity of cereals and of undertaking research in this area. Candidate components other than gluten include poorly absorbed oligosaccharides (mainly fructans), non-gluten wheat proteins such as amylase-trypsin inhibitors or wheat germ agglutinin, and exorphins released during the digestion of gluten. Specific biological and/or clinical effects associated with gluten-free diets or wheat ingestion need to be carefully dissected before attribution to gluten can be claimed. Conclusions: Currently, coeliac disease is the only common condition that has been unequivocally linked to gluten. Inaccurate attribution will be associated with suboptimal therapeutic advice and at least partly underlies the current gluten-free epidemic gripping the Western world.

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Effects of wheat germ agglutinin on human gastrointestinal epithelium: Insights from an experimental model of immune/epithelial cell interaction

Cited by 67 publications

References 35 publications

Non-Celiac Gluten Sensitivity: A Challenging Diagnosis in Children with Abdominal Pain

Non-Celiac Gluten Sensitivity: A Challenging Diagnosis in Children with Abdominal Pain

The spectrum of noncoeliac gluten sensitivity

Other Dietary Confounders: FODMAPS et al.

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