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A Food-Grade Enzyme Preparation with Modest Gluten Detoxification Properties
BACKGROUND AND AIMS: Celiac sprue is a life-long disease characterized by an intestinal inflammatory response to dietary gluten. A gluten-free diet is an effective treatment for most patients, but accidental ingestion of gluten is common, leading to incomplete recovery or relapse. Food-grade proteas...
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Formato: | Texto |
Lenguaje: | English |
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Public Library of Science
2009
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2708912/ https://www.ncbi.nlm.nih.gov/pubmed/19621078 http://dx.doi.org/10.1371/journal.pone.0006313 |
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author | Ehren, Jennifer Morón, Belen Martin, Edith Bethune, Michael T. Gray, Gary M. Khosla, Chaitan |
author_facet | Ehren, Jennifer Morón, Belen Martin, Edith Bethune, Michael T. Gray, Gary M. Khosla, Chaitan |
author_sort | Ehren, Jennifer |
collection | PubMed |
description | BACKGROUND AND AIMS: Celiac sprue is a life-long disease characterized by an intestinal inflammatory response to dietary gluten. A gluten-free diet is an effective treatment for most patients, but accidental ingestion of gluten is common, leading to incomplete recovery or relapse. Food-grade proteases capable of detoxifying moderate quantities of dietary gluten could mitigate this problem. METHODS: We evaluated the gluten detoxification properties of two food-grade enzymes, aspergillopepsin (ASP) from Aspergillus niger and dipeptidyl peptidase IV (DPPIV) from Aspergillus oryzae. The ability of each enzyme to hydrolyze gluten was tested against synthetic gluten peptides, a recombinant gluten protein, and simulated gastric digests of whole gluten and whole-wheat bread. Reaction products were analyzed by mass spectrometry, HPLC, ELISA with a monoclonal antibody that recognizes an immunodominant gluten epitope, and a T cell proliferation assay. RESULTS: ASP markedly enhanced gluten digestion relative to pepsin, and cleaved recombinant α2-gliadin at multiple sites in a non-specific manner. When used alone, neither ASP nor DPPIV efficiently cleaved synthetic immunotoxic gluten peptides. This lack of specificity for gluten was especially evident in the presence of casein, a competing dietary protein. However, supplementation of ASP with DPPIV enabled detoxification of moderate amounts of gluten in the presence of excess casein and in whole-wheat bread. ASP was also effective at enhancing the gluten-detoxifying efficacy of cysteine endoprotease EP-B2 under simulated gastric conditions. CONCLUSIONS: Clinical studies are warranted to evaluate whether a fixed dose ratio combination of ASP and DPPIV can provide near-term relief for celiac patients suffering from inadvertent gluten exposure. Due to its markedly greater hydrolytic activity against gluten than endogenous pepsin, food-grade ASP may also augment the activity of therapeutically relevant doses of glutenases such as EP-B2 and certain prolyl endopeptidases. |
format | Text |
id | pubmed-2708912 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-27089122009-07-21 A Food-Grade Enzyme Preparation with Modest Gluten Detoxification Properties Ehren, Jennifer Morón, Belen Martin, Edith Bethune, Michael T. Gray, Gary M. Khosla, Chaitan PLoS One Research Article BACKGROUND AND AIMS: Celiac sprue is a life-long disease characterized by an intestinal inflammatory response to dietary gluten. A gluten-free diet is an effective treatment for most patients, but accidental ingestion of gluten is common, leading to incomplete recovery or relapse. Food-grade proteases capable of detoxifying moderate quantities of dietary gluten could mitigate this problem. METHODS: We evaluated the gluten detoxification properties of two food-grade enzymes, aspergillopepsin (ASP) from Aspergillus niger and dipeptidyl peptidase IV (DPPIV) from Aspergillus oryzae. The ability of each enzyme to hydrolyze gluten was tested against synthetic gluten peptides, a recombinant gluten protein, and simulated gastric digests of whole gluten and whole-wheat bread. Reaction products were analyzed by mass spectrometry, HPLC, ELISA with a monoclonal antibody that recognizes an immunodominant gluten epitope, and a T cell proliferation assay. RESULTS: ASP markedly enhanced gluten digestion relative to pepsin, and cleaved recombinant α2-gliadin at multiple sites in a non-specific manner. When used alone, neither ASP nor DPPIV efficiently cleaved synthetic immunotoxic gluten peptides. This lack of specificity for gluten was especially evident in the presence of casein, a competing dietary protein. However, supplementation of ASP with DPPIV enabled detoxification of moderate amounts of gluten in the presence of excess casein and in whole-wheat bread. ASP was also effective at enhancing the gluten-detoxifying efficacy of cysteine endoprotease EP-B2 under simulated gastric conditions. CONCLUSIONS: Clinical studies are warranted to evaluate whether a fixed dose ratio combination of ASP and DPPIV can provide near-term relief for celiac patients suffering from inadvertent gluten exposure. Due to its markedly greater hydrolytic activity against gluten than endogenous pepsin, food-grade ASP may also augment the activity of therapeutically relevant doses of glutenases such as EP-B2 and certain prolyl endopeptidases. Public Library of Science 2009-07-21 /pmc/articles/PMC2708912/ /pubmed/19621078 http://dx.doi.org/10.1371/journal.pone.0006313 Text en Ehren et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Ehren, Jennifer Morón, Belen Martin, Edith Bethune, Michael T. Gray, Gary M. Khosla, Chaitan A Food-Grade Enzyme Preparation with Modest Gluten Detoxification Properties |
title | A Food-Grade Enzyme Preparation with Modest Gluten Detoxification Properties |
title_full | A Food-Grade Enzyme Preparation with Modest Gluten Detoxification Properties |
title_fullStr | A Food-Grade Enzyme Preparation with Modest Gluten Detoxification Properties |
title_full_unstemmed | A Food-Grade Enzyme Preparation with Modest Gluten Detoxification Properties |
title_short | A Food-Grade Enzyme Preparation with Modest Gluten Detoxification Properties |
title_sort | food-grade enzyme preparation with modest gluten detoxification properties |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2708912/ https://www.ncbi.nlm.nih.gov/pubmed/19621078 http://dx.doi.org/10.1371/journal.pone.0006313 |
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