title: 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.
  
  
  OBJECTIVE
  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 α-gliadin concentration AUC0-240 min, compared to placebo, from low and high calorie meals in stomach (low: 35 vs. 389 μg × min/mL; high: 53 vs. 386 μg × min/mL; P < 0.001) and duodenum (low: 7 vs. 168 μg × min/mL; high: 4 vs. 32 μg × min/mL; P < 0.001) and absolute α-gliadin AUC0-240 min in the duodenum from low (2813 vs. 31 952 μg × min; P < 0.001) and high (2553 vs. 13 095 μg × min; P = 0.013) calorie meals. In the placebo group, the high compared to low calorie meal slowed gastric emptying and lowered the duodenal α-gliadin concentration AUC0-240 min (32 vs. 168 μg × 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.
authors.affiliation: Division of Gastroenterology-Hepatology, Department of Internal Medicine, NUTRIM, Maastricht University Medical Center (MUMC+), Maastricht, The Netherlands.
authors.forename: B N
authors.initials: BN
authors.lastname: Salden
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Centre (LUMC), Leiden, The Netherlands.
authors.forename: V
authors.initials: V
authors.lastname: Monserrat
authors.affiliation: Division of Gastroenterology-Hepatology, Department of Internal Medicine, NUTRIM, Maastricht University Medical Center (MUMC+), Maastricht, The Netherlands.
authors.forename: F J
authors.initials: FJ
authors.lastname: Troost
authors.affiliation: DSM Biotechnology Centre, Delft, The Netherlands.
authors.forename: M J
authors.initials: MJ
authors.lastname: Bruins
authors.affiliation: DSM Biotechnology Centre, Delft, The Netherlands.
authors.forename: L
authors.initials: L
authors.lastname: Edens
authors.affiliation: Department of Pharmacology and Toxicology, CARIM, Maastricht University, Maastricht, The Netherlands.
authors.forename: R
authors.initials: R
authors.lastname: Bartholomé
authors.affiliation: Department of Pharmacology and Toxicology, CARIM, Maastricht University, Maastricht, The Netherlands.
authors.forename: G R
authors.initials: GR
authors.lastname: Haenen
authors.affiliation: Department of Methodology and Statistics, CAPHRI, Maastricht University Medical Center (MUMC+), Maastricht, The Netherlands.
authors.forename: B
authors.initials: B
authors.lastname: Winkens
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Centre (LUMC), Leiden, The Netherlands.
authors.forename: F
authors.initials: F
authors.lastname: Koning
authors.affiliation: Division of Gastroenterology-Hepatology, Department of Internal Medicine, NUTRIM, Maastricht University Medical Center (MUMC+), Maastricht, The Netherlands.
authors.forename: A A
authors.initials: AA
authors.lastname: Masclee
mesh_terms: D000082:Acetaminophen / Q000378:metabolism; D000328:Adult; D001234:Aspergillus niger / Q000201:enzymology*; D018592:Cross-Over Studies; D004063:Digestion / Q000502:physiology; D004311:Double-Blind Method; D004386:Duodenum / Q000378:metabolism; D002149:Energy Intake / Q000502:physiology*; D005260:Female; D005746:Gastric Emptying / Q000502:physiology; D005753:Gastric Mucosa / Q000378:metabolism; D005903:Gliadin / Q000378:metabolism; D005983:Glutens / Q000378:metabolism*; D006801:Humans; D008297:Male; D055815:Young Adult
chemical_list: D000082:Acetaminophen; D005983:Glutens; D005903:Gliadin