Next-generation therapies for celiac disease: The gluten-targeted approaches

Ribeiro, Miguel; Nunes, Fernando M.; Rodríguez-Quijano, Marta; Carrillo, José M.; Branlard, Gérard; Igrejas, Gilberto

doi:10.1016/j.tifs.2018.02.021

Cited by 44 publications

(42 citation statements)

References 129 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Our own research and parallel studies performed elsewhere clearly showed that it is possible to obtain ‘reduced-gluten wheat genotypes/varieties’ (Wen et al 2012; also cf. Ribeiro et al 2018). These lines are neither fully depleted of gluten nor do they completely lack the well-known highly immunogenic gluten peptides, except the recently developed wheat lines that lack highly immunogenic 33-mer gliadin peptide (Sánchez-León et al 2018).…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, previously established lines still contained higher molecular weight (HMW) glutenins, which are indispensable for baking and were thus far supposed to be largely non-immunogenic. However, there is a small proportion of celiac patients who showed sensitivity to HMW glutenins and could not consume wheat genotypes containing these proteins (Barro et al 2016; Ribeiro et al 2018). …”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Development of wheat genotypes expressing a glutamine-specific endoprotease from barley and a prolyl endopeptidase from Flavobacterium meningosepticum or Pyrococcus furiosus as a potential remedy to celiac disease

Osorio

Wen

Mejías

et al. 2018

Funct Integr Genomics

View full text Add to dashboard Cite

Ubiquitous nature of prolamin proteins dubbed gluten from wheat and allied cereals imposes a major challenge in the treatment of celiac disease, an autoimmune disorder with no known treatment other than abstinence diet. Administration of hydrolytic glutenases as food supplement is an alternative to deliver the therapeutic agents directly to the small intestine, where sensitization of immune system and downstream reactions take place. The aim of the present research was to evaluate the capacity of wheat grain to express and store hydrolytic enzymes capable of gluten detoxification. For this purpose, wheat scutellar calli were biolistically transformed to generate plants expressing a combination of glutenase genes for prolamin detoxification. Digestion of prolamins with barley endoprotease B2 (EP-HvB2) combined with Flavobacterium meningosepticum prolyl endopeptidase (PE-FmPep) or Pyrococcus furiosus prolyl endopeptidase (PE-PfuPep) significantly reduced (up to 67%) the amount of the indigestible gluten peptides of all prolamin families tested. Seven of the 168 generated lines showed inheritance of transgene to the T generation. Reversed phase high-performance liquid chromatography of gluten extracts under simulated gastrointestinal conditions allowed the identification of five T lines that contained significantly reduced amounts of immunogenic, celiac disease-provoking gliadin peptides. These findings were complemented by the R5 ELISA test results where up to 72% reduction was observed in the content of immunogenic peptides. The developed wheat genotypes open new horizons for treating celiac disease by an intraluminal enzyme therapy without compromising their agronomical performance.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Development of wheat genotypes expressing a glutamine-specific endoprotease from barley and a prolyl endopeptidase from Flavobacterium meningosepticum or Pyrococcus furiosus as a potential remedy to celiac disease

Osorio

Wen

Mejías

et al. 2018

Funct Integr Genomics

View full text Add to dashboard Cite

show abstract

“…More extensive studies were carried out by Barro and coworkers (Table 2). This work has been reviewed in detail (García-Molina, Giménez, Sánchez-León, & Barro, 2019;Gilissen et al, 2014;Jouanin, Boyd, Visser, & Smulders, 2018;Ribeiro et al, 2018;Rosella et al, 2014;Shewry & Tatham, 2016) and is therefore discussed only briefly here. In summary, they generated two series of lines, with downregulation of only γ -gliadins (Gil-Humanes et al, 2008;Piston, Gil-Humanes, Rodríguez-Quijano, & Barro, 2011) or all gliadins (α/β-, γ -, and ω-) and LMW subunits (Gil-Humanes, Piston, Shewry, Tosi, & Barro, 2011;Gil-Humanes, Piston, Tollefsen, Sollid, & Barro, 2010).…”

Section: Use Of Genetic Modification To Develop Coeliac-safe Wheat Gementioning

confidence: 99%

Wheat Seed Proteins: Factors Influencing Their Content, Composition, and Technological Properties, and Strategies to Reduce Adverse Reactions

Rustgi

Shewry

Brouns

et al. 2019

Comp Rev Food Sci Food Safe

View full text Add to dashboard Cite

Wheat is the primary source of nutrition for many, especially those living in developing countries, and wheat proteins are among the most widely consumed dietary proteins in the world. However, concerns about disorders related to the consumption of wheat and/or wheat gluten proteins have increased sharply in the last 20 years. This review focuses on wheat gluten proteins and amylase trypsin inhibitors, which are considered to be responsible for eliciting most of the intestinal and extraintestinal symptoms experienced by susceptible individuals. Although several approaches have been proposed to reduce the exposure to gluten or immunogenic peptides resulting from its digestion, none have proven sufficiently effective for general use in coeliac‐safe diets. Potential approaches to manipulate the content, composition, and technological properties of wheat proteins are therefore discussed, as well as the effects of using gluten isolates in various food systems. Finally, some aspects of the use of gluten‐free commodities are discussed.

show abstract

“…Therefore, several strategies have been developed in order to detoxify the gluten and make it potentially safe for celiac patients such as the degradation of immunodominant peptides by specific proteases, the development of genetically modified low‐gliadin wheat lines and the previous transamidation of glutamine residues present in gluten proteins in order to hamper its deamidation by human tissue transglutaminase . However, in general these strategies result in a decrease in gluten functionality and in particular for the genetically modified low‐gliadin wheat lines there are still doubts associated with dealing with genetically modified organisms …”

Section: Introductionmentioning

confidence: 99%

In Situ Gluten–Chitosan Interlocked Self‐Assembled Supramolecular Architecture Reduces T‐Cell‐Mediated Immune Response to Gluten in Celiac Disease

Ribeiro

Picascia

Rhazi

et al. 2018

Molecular Nutrition Food Res

Self Cite

View full text Add to dashboard Cite

Scope The prevalence of celiac disease has increased since the last half of the 20th century and is now about 1% in most western populations. At present, people who suffer from celiac disease have to follow a gluten‐exclusion diet throughout their lives. Compliance to this restrictive diet is demanding and the development of alternative strategies has become urgent. Methods and results In this context, it is found that the biocompatible aminopolysaccharide chitosan imposes a different gluten reorganization after gluten redox reaction producing in situ mechanically interlocked supramolecular assemblies between gluten and chitosan. These new structures result in the decrease of gluten digestibility, tissue transglutaminase deamidation activity, and interferon‐γ production in intestinal T cell lines generated from biopsy specimens of celiac disease patients. Conclusion Overall, the results demonstrate the potential of this research avenue to celiac disease is problematic, as the reorganization of gluten proteins to a novel supramolecular architecture shows a positive impact on known pathogenesis mechanisms of the disease. At present, the only therapy for celiac disease is adherence to a gluten‐free diet. Here, it is shown that chitosan‐imposed gluten reorganization to an interlocked self‐assembled supramolecular architecture reduces gluten digestibility, R5‐reactivity, tissue transglutaminase deamidation activity, and its capacity to stimulate a T‐cell‐mediated immune response in celiac disease.

show abstract

Next-generation therapies for celiac disease: The gluten-targeted approaches

Cited by 44 publications

References 129 publications

Development of wheat genotypes expressing a glutamine-specific endoprotease from barley and a prolyl endopeptidase from Flavobacterium meningosepticum or Pyrococcus furiosus as a potential remedy to celiac disease

Development of wheat genotypes expressing a glutamine-specific endoprotease from barley and a prolyl endopeptidase from Flavobacterium meningosepticum or Pyrococcus furiosus as a potential remedy to celiac disease

Wheat Seed Proteins: Factors Influencing Their Content, Composition, and Technological Properties, and Strategies to Reduce Adverse Reactions

In Situ Gluten–Chitosan Interlocked Self‐Assembled Supramolecular Architecture Reduces T‐Cell‐Mediated Immune Response to Gluten in Celiac Disease

Contact Info

Product

Resources

About