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Randomised clinical study: Aspergillus niger-derived enzyme digests gluten in the stomach of healthy volunteers.

ABSTRACT: BACKGROUND:Aspergillus niger prolyl endoprotease (AN-PEP) efficiently degrades gluten molecules into non-immunogenic peptides in vitro. AIM:To assess the efficacy of AN-PEP on gluten degradation in a low and high calorie meal in healthy subjects. METHODS:In this randomised, double-blind, placebo-controlled, cross-over study 12 healthy volunteers attended to four test days. A liquid low or high calorie meal (4 g gluten) with AN-PEP or placebo was administered into the stomach. Via a triple-lumen catheter gastric and duodenal aspirates were sampled, and polyethylene glycol (PEG)-3350 was continuously infused. Acetaminophen in the meals tracked gastric emptying time. Gastric and duodenal samples were used to calculate 240-min area under the curve (AUC0-240 min ) of ?-gliadin concentrations. Absolute ?-gliadin AUC0-240 min was calculated using duodenal PEG-3350 concentrations. RESULTS:AN-PEP lowered ?-gliadin concentration AUC0-240 min, compared to placebo, from low and high calorie meals in stomach (low: 35 vs. 389 ?g × min/mL; high: 53 vs. 386 ?g × min/mL; P < 0.001) and duodenum (low: 7 vs. 168 ?g × min/mL; high: 4 vs. 32 ?g × min/mL; P < 0.001) and absolute ?-gliadin AUC0-240 min in the duodenum from low (2813 vs. 31 952 ?g × min; P < 0.001) and high (2553 vs. 13 095 ?g × min; P = 0.013) calorie meals. In the placebo group, the high compared to low calorie meal slowed gastric emptying and lowered the duodenal ?-gliadin concentration AUC0-240 min (32 vs. 168 ?g × min/mL; P = 0.001). CONCLUSIONS:AN-PEP significantly enhanced gluten digestion in the stomach of healthy volunteers. Increasing caloric density prolonged gastric residence time of the meal. Since AN-PEP already degraded most gluten from low calorie meals, no incremental effect was observed by increasing meal caloric density. ClinicalTrials.gov, Number: NCT01335503; www.trialregister.nl, Number: NTR2780.

SUBMITTER: Salden BN

PROVIDER: S-EPMC5032996 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature

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Randomised clinical study: Aspergillus niger-derived enzyme digests gluten in the stomach of healthy volunteers.

Salden B N BN Monserrat V V Troost F J FJ Bruins M J MJ Edens L L Bartholomé R R Haenen G R GR Winkens B B Koning F F Masclee A A AA

Alimentary pharmacology & therapeutics 20150604 3

<h4>Background</h4>Aspergillus niger prolyl endoprotease (AN-PEP) efficiently degrades gluten molecules into non-immunogenic peptides in vitro.<h4>Aim</h4>To assess the efficacy of AN-PEP on gluten degradation in a low and high calorie meal in healthy subjects.<h4>Methods</h4>In this randomised, double-blind, placebo-controlled, cross-over study 12 healthy volunteers attended to four test days. A liquid low or high calorie meal (4 g gluten) with AN-PEP or placebo was administered into the stomac ...[more]

PMID: 26040627

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Project description:BackgroundFilamentous fungi such as Aspergillus niger have a high capacity secretory system and are therefore widely exploited for the industrial production of native and heterologous proteins. However, in most cases the yields of non-fungal proteins are significantly lower than those obtained for fungal proteins. One well-studied bottleneck appears to be the result of mis-folding of heterologous proteins in the ER during early stages of secretion, with related stress responses in the host, including the unfolded protein response (UPR). This study aims at uncovering transcriptional and translational responses occurring in A. niger exposed to secretion stress.ResultsA genome-wide transcriptional analysis of protein secretion-related stress responses was determined using Affymetrix DNA GeneChips and independent verification for selected genes. Endoplasmic reticulum (ER)-associated stress was induced either by chemical treatment of the wild-type cells with dithiothreitol (DTT) or tunicamycin, or by expressing a human protein, tissue plasminogen activator (t-PA). All of these treatments triggered the UPR, as shown by the expression levels of several well-known UPR target genes. The predicted proteins encoded by most of the up-regulated genes function as part of the secretory system including chaperones, foldases, glycosylation enzymes, vesicle transport proteins, and ER-associated degradation proteins. Several genes were down-regulated under stress conditions and these included several genes that encode secreted enzymes. Moreover, translational regulation under ER stress was investigated by polysomal fractionation. This analysis confirmed the post-transcriptional control of hacA expression and highlighted that differential translation also occurs during ER stress, in particular for some genes encoding secreted proteins or proteins involved in ribosomal biogenesis and assembly.ConclusionThis is first genome-wide analysis of both transcriptional and translational events following protein secretion stress. Insight has been gained into the molecular basis of protein secretion and secretion-related stress in an effective protein-secreting fungus, and provides an opportunity to identify target genes for manipulation in strain improvement strategies.

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Randomised clinical study: Aspergillus niger-derived enzyme digests gluten in the stomach of healthy volunteers.

Publications

Randomised clinical study: Aspergillus niger-derived enzyme digests gluten in the stomach of healthy volunteers.

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