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

Aliment Pharmacol Ther. 2015 Aug;42(3):273-85. doi: 10.1111/apt.13266. Epub 2015 Jun 4.


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 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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetaminophen / metabolism
  • Adult
  • Aspergillus niger / enzymology*
  • Cross-Over Studies
  • Digestion / physiology
  • Double-Blind Method
  • Duodenum / metabolism
  • Energy Intake / physiology*
  • Female
  • Gastric Emptying / physiology
  • Gastric Mucosa / metabolism
  • Gliadin / metabolism
  • Glutens / metabolism*
  • Humans
  • Male
  • Young Adult


  • Acetaminophen
  • Glutens
  • Gliadin

Associated data

  • NTR/NTR2780
  • ClinicalTrials.gov/NCT01335503