Combination enzyme therapy for gastric digestion of dietary gluten in patients with celiac sprue |
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Authors: | Gass Jonathan Bethune Michael T Siegel Matthew Spencer Andrew Khosla Chaitan |
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Institution: | Department of Chemical Engineering, Stanford University, Stanford, California, USA. |
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Abstract: | BACKGROUND AND AIMS: Celiac sprue is a multifactorial disease characterized by an inflammatory response to ingested gluten in the small intestine. Proteolytically resistant, proline- and glutamine-rich gluten peptides from wheat, rye, and barley persist in the intestinal lumen and elicit an immune response in genetically susceptible persons. We investigated a new combination enzyme product, consisting of a glutamine-specific endoprotease (EP-B2 from barley) and a prolyl endopeptidase (SC PEP from Sphingomonas capsulata), for its ability to digest gluten under gastric conditions. METHODS: The ability of this combination enzyme to digest and detoxify whole-wheat bread gluten was investigated. In vitro and in vivo (rat) experimental systems were developed to simulate human gastric digestion, and the resulting material was analyzed by high-performance liquid chromatography, enzyme-linked immunoabsorbent assay, and patient-derived T-cell proliferation assays. RESULTS: The analysis revealed that EP-B2 extensively proteolyzes complex gluten proteins in bread, whereas SC PEP rapidly detoxifies the residual oligopeptide products of EP-B2 digestion. In vitro dose variation data suggests that an approximate 1:1 weight ratio of the 2 enzymes should maximize their synergistic potential. The efficacy of this 2-enzyme glutenase was verified in a rat model of gastric gluten digestion. CONCLUSIONS: By combining 2 enzymes with gastric activity and complementary substrate specificity, it should be possible to increase the safe threshold of ingested gluten, thereby ameliorating the burden of a highly restricted diet for patients with celiac sprue. |
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Keywords: | ELISA enzyme-linked immunoabsorbent assay EP-B2 endoprotease B isoform 2 from Hordeum vulgare HPLC high-performance liquid chromatography PEP prolyl endopeptidase PTC pepsin trypsin chymotrypsin SC Sphingomonas capsulate |
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