Gut 57:25-32 doi:10.1136/gut.2006.111609
  • Coeliac disease

Efficient degradation of gluten by a prolyl endoprotease in a gastrointestinal model: implications for coeliac disease

  1. C Mitea1,
  2. R Havenaar2,
  3. J Wouter Drijfhout1,
  4. L Edens3,
  5. L Dekking1,
  6. F Koning1
  1. 1
    Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, the Netherlands
  2. 2
    TNO Quality of Life, Zeist, the Netherlands
  3. 3
    DSM Food Specialties, Delft, the Netherlands
  1. Dr E H A Dekking, Department of Immunohematology and Blood Transfusion, E3-Q, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands; e.h.a.dekking{at}
  • Revised 8 March 2007
  • Accepted 24 April 2007
  • Published Online First 9 May 2007


Background: Coeliac disease is caused by an immune response to gluten. As gluten proteins are proline rich they are resistant to enzymatic digestion in the gastrointestinal tract, a property that probably contributes to the immunogenic nature of gluten.

Aims: This study determined the efficiency of gluten degradation by a post-proline cutting enzyme, Aspergillus niger prolyl endoprotease (AN-PEP), in a dynamic system that closely mimics the human gastrointestinal tract (TIM system).

Methods: Two experiments were performed. In the first, a slice of bread was processed in the TIM system with and without co-administration of AN-PEP. In the second, a standard fast food menu was used. Samples of the digesting meals were taken from the stomach, duodenum, jejunum and ileum compartments at time zero until 4 hours after the start of the experiment. In these samples the levels of immunogenic peptides from gliadins and glutenins were assessed by monoclonal antibody-based competition assays, Western blot analysis and proliferation T-cell assays.

Results: AN-PEP accelerated the degradation of gluten in the stomach compartment to such an extent that hardly any gluten reached the duodenum compartment.

Conclusion: AN-PEP is capable of accelerating the degradation of gluten in a gastrointestinal system that closely mimics in-vivo digestion. This implies that the co-administration of AN-PEP with a gluten-containing meal might eliminate gluten toxicity, thus offering patients the possibility of abandoning (occasionally) their strict gluten-free diet.


  • Funding: This study was supported by the Celiac Disease Consortium, an Innovative Cluster approved by the Netherlands Genomics Initiative and partly funded by the Dutch Government (BSIK03009)

  • Competing interests: Declared (the declaration can be viewed on the Gut website at