Celiac Disease: Advances in Treatment via Gluten Modification

doi:10.1016/j.cgh.2012.06.005

Clinical Gastroenterology and Hepatology

Volume 10, Issue 8, August 2012, Pages 859-862

https://doi.org/10.1016/j.cgh.2012.06.005 Get rights and content

Celiac disease (CD) is an autoimmune enteropathy that occurs in genetically susceptible individuals carrying the prerequisite genetic markers HLA DQ2 or DQ8. These genetic markers are present in approximately 30% of the population, and the worldwide prevalence of CD is estimated to be approximately 1%–2%. Currently a gluten-free diet is the only treatment for CD, but novel therapies aimed at gluten modification are underway. This review will discuss gluten-based therapies including wheat alternatives and wheat selection, enzymatic alteration of wheat, oral enzyme supplements, and polymeric binders as exciting new therapies for treatment of CD.

Section snippets

Gluten replacement

One gluten-based therapeutic approach is to use grains that do not have the immunogenic proteins found in wheat-derived gluten (Figure 1). One such grain that has garnered some interest as a wheat substitute is sorghum, which is a cereal grain related to maize. It has been consumed for thousands of years in Africa and Asia. More recently, sorghum has been used to make multiple wheat-free products, including breads, tortillas, cookies, and flatbreads that do not have discolorations or odd

What Are the Roadblocks and/or Limitations?

Roadblocks and limitations to the clinical application of the aforementioned products (genetically altered wheat, enzymatically altered wheat, oral enzyme supplements, and polymeric binders) are the tests to measure their safety and efficacy. The ideal gold standard would be to perform serology and histology on all patients; however, the problems with this approach include cost, patient time/comfort, and availability of resources (ie, endoscopy suites and staffing, available pathologists).⁵

Conclusions

CD is a common immune enteropathy affecting approximately 1% of the world's population. Currently, the only treatment available is a GFD that is wrought with multiple issues including inconsistent definitions in different countries, gluten contamination, cost, and availability. As many as 50% of patients adherent to a GFD will not achieve histologic remission; this is likely due to hidden gluten contamination. Further advances in genetically altering wheat varieties may make a GFD easier. In

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Cited by (42)

Clinical manifestations of gastrointestinal diseases in the oral cavity
2021, Saudi Dental Journal
Citation Excerpt :
Atypical symptoms of CeD include some extra-intestinal manifestations, such as abnormal liver function, anemia, osteoporosis, neurological problems, and dental problems (Pastore, et al., 2008a, Pastore, et al., 2008b, Gujral, et al., 2012). Currently, the only effective treatment available for CeD is adopting a gluten-free diet (Stoven, et al., 2012). Several oral symptoms have been reported in CeD patients, including dental enamel defects (Pastore, et al., 2008b, Cheng, et al., 2010, Ouda, et al., 2010) and oral ulcers (Cheng, et al., 2010, Ouda, et al., 2010, Baccaglini, et al., 2011).
In this review, several gastrointestinal diseases that dentists may encounter in practice are highlighted and discussed.
Using MEDLINE (PubMed), a comprehensive review of gastrointestinal diseases and their oral cavity manifestations was performed.
Many gastrointestinal diseases present with oral symptoms that are detectable by dentists and dental hygienists. Often, oral manifestations of the disease may appear before systemic signs and symptoms. Managing patients with these conditions requires dentists to adjust their treatment and/or involve other health professionals.
Care must be taken when providing periodontal therapy or dental implants to patients suffering gastrointestinal diseases who are at high risk of bleeding, infection, or malnutrition, for example. Also, pharmacological therapy for these patients may need to be customized.
Oral enzyme strategy in celiac disease
2021, Biotechnological Strategies for the Treatment of Gluten Intolerance
A gluten-free diet (GFD) is currently the only effective treatment for celiac disease (CD). However, GFD is restrictive, and several studies have reported high levels of dietary transgressions in CD patients. Development of alternative therapies is ongoing, with the most clinically advanced therapies focusing on detoxifying immunogenic gluten fragments in the gastric and upper intestinal tracts, thereby avoiding intestinal mucosal damage. In this chapter, we summarize the enzymes, termed glutenases, capable of variably degrading proline- and glutamine-rich residues of gluten peptides. The use of these endoproteases as therapeutic agents has been proposed as a viable therapy for CD, aiming to establish an optimal oral dose that would not induce detectable and clinically significant mucosal deterioration over time. Although this appears promising, it may be, at best, used as an oral supplement, rather than a replacement, to GFD.
Gluten peptide immunomodulatory strategies
2021, Biotechnological Strategies for the Treatment of Gluten Intolerance
Therapeutic vaccines based on the administration of causative antigenic peptides have shown successful results in the desensitization of adverse immune reaction in allergic and autoimmune diseases. Since the peptide-based immunomodulatory strategy utilizes immunodominant epitopes to elicit regulatory pathways instead of the activation of disease-triggering T cells, the identification of the whole repertoire of pathogenic antigenic peptides is required to implement the therapy.
Celiac disease is an autoimmune disorder caused by a dysregulated T-cell response to gluten proteins. Recent studies have comprehensively defined the gluten peptides responsible for the intestinal inflammatory reaction in both children and adults, thus opening realistic prospective for an antigen-based immunomodulatory therapy in celiac disease patients.
This review will examine the proof of principle and state of the art of gluten peptide vaccine as an immunomodulatory drug to treat gluten intolerance.
Proteases as digestive aids
2018, Encyclopedia of Food Chemistry
The human digestive system is a complex organ containing millions of different cell types. These cells develop, interact and communicate in a complicated and regulated process, exhibiting notable plasticity. Proteolytic enzymes, or proteases, that are secreted in different regions of the digestive tract, i.e. the stomach, pancreas and small intestine, play a major role in protein digestion. Abnormal levels of proteases can lead to clinical conditions, such as inflammatory bowel disease (IBD), irritable bowel syndrome (IBS) and nutrient malabsorption. Protease enzyme therapy is a treatment option to restore pancreatic activity and/or digest ingested proteins in the digestive tract. This chapter provides an overview of the different types of endogenous proteases in the gastrointestinal tract, exogenous sources, and a summary of current knowledge of select disease conditions, for example, pancreatic insufficiency and celiac disease, where supplementary protease therapy show promise as a treatment option.
Celiac Disease
2017, Foodborne Diseases: Third Edition
With a worldwide prevalence of about 1%, celiac disease is the most common food intolerance globally. The condition is thought to have emerged during the time when humans transitioned from hunter-gatherer groups to societies that relied on agriculture. Despite its high prevalence, celiac disease is estimated to remain unrecognized in up to 90% of individuals from Western countries. It is a life-long condition that involves genetic and environmental predisposition factors, which interact in a complex fashion with the immune system. Celiac disease is the only known autoimmune condition for which the environmental and the genetic predisposition factors have both been identified, and their interaction with the immune system has been thoroughly characterized at the molecular and cellular levels. While the prevalence of celiac disease varies with gender and geographic location, the condition affects individuals at any age and is characterized by signs and symptoms that extend beyond the gastrointestinal tract. The multifactorial presentation of celiac disease opens diagnostic challenges in both children and adults. Advances in serological testing have improved the management of celiac disease, and, in recent years, diagnosis can be performed in some patient groups without the need for intestinal biopsies. The only effective treatment remains a life-long gluten-free diet. Even though gluten avoidance improves the quality of life and decreases the risk of comorbidities, celiac disease is associated with a life-long burden for patients and families. Nevertheless, contamination and limited compliance, along with persistent or recurrent symptoms in patients with refractory disease, make novel therapeutic strategies a major need in the field.
Development of hyoimmunogenic pasta and its immunochemical validation with celiac disease patients' sera
2015, LWT
Citation Excerpt :
Since several years new therapeutic approaches have been carried out to modify the immunogenic sequences of gluten peptides so as to detoxify them and to use it in foods for CD patients (Cabrera-Chavez & de la Barca, 2010). Gluten replacement and gluten removal are among such novel approaches (Stoven et al., 2012). Modifying harmful immunogenic epitopes genetically has been considered as another novel approach and desired therapeutic option.
The present study was carried out with an aim to develop low immunogenic pasta by altering the pH of Triticum durum flour and immunological validation of pasta using patients' sera. Modification of T. durum wheat flour was carried out by altering pH of the flour using lactic acid, sodium bicarbonate and natural ingredients such as tomato, spinach puree. The pH altered flours were taken for rheological studies and also extruded into pasta using lab scale extruder. Pasta quality characteristics were analyzed and Celiac disease patients' sera was used for immunological validation of pasta. Immunoreactivity of alkaline modified pasta with IgA anti-gliadin antibodies of patients' sera was markedly reduced than control and acid modified pasta as indicated by both Dot-Blot and ELISA. Quality evaluation showed the acceptable and comparable product quality parameters. The study indicated that altering the pH of wheat flour chemically to pH 9.00 is effective in reducing immunogenic property of wheat flour and comparable quality pasta thus developed pasta could be beneficial for patients with celiac disease. However modification occurring at epitope structure of gliadin due to alkaline condition and safety on long term consumption of this product needs to be evaluated further.

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: Conflicts of interest This author discloses the following: Joseph Murray has been a consultant to Alvine Inc. The remaining authors disclose no conflicts.

: Funding Supported in part by grants DK 57892 and DK071003 from the National Institute of Health (J.A.M).

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Advances in translational scienceCeliac Disease: Advances in Treatment via Gluten Modification

Section snippets

Gluten replacement

What Are the Roadblocks and/or Limitations?

Conclusions

Dig Liver Dis

Gastroenterology

Clin Immunol

Gastroenterology

Am J Clin Nutr

Clin Nutr

Gastroenterology

Clin Gastroenterol Hepatol

Gastroenterology

Removing celiac disease-related gluten proteins from bread wheat while retaining technological properties: a study with Chinese Spring deletion lines

BMC Plant Biol

Wheat deficient in gliadins: promising tool for treatment of coeliac disease

Gut

A food-grade enzyme preparation with modest gluten detoxification properties

PLoS ONE

Advances in translational science
Celiac Disease: Advances in Treatment via Gluten Modification