Effect of pretreatment of food gluten with prolyl endopeptidase on gluten-induced malabsorption in celiac sprue

Clin Gastroenterol Hepatol. 2005 Jul;3(7):687-94. doi: 10.1016/s1542-3565(05)00366-6.


Background & aims: We sought to determine whether prolyl endopeptidase (PEP) treatment of food gluten would obviate the intestinal dysfunction produced by small amounts of dietary gluten supplement in patients with celiac sprue.

Methods: Twenty asymptomatic patients with histologically proven celiac sprue completed a randomized, double-blind, cross-over study involving two 14-day stages. Each patient consumed a low dose of a gluten supplement daily (5 g; equivalent to 1 slice of bread) in 1 stage and gluten pretreated with PEP in the other stage. Patients completed a daily symptom questionnaire and a D-xylose urine excretion and a 72-hour quantitative fecal fat were monitored before and after each stage.

Results: Despite clinical remission at baseline, 40% of patients had at least 1 abnormal celiac antibody, 20% had an abnormal urine xylose, and 63% had an abnormal fecal fat test result. There was no difference in symptoms as a function of the type of gluten consumed. In response to gluten not treated with PEP, an appreciable proportion of patients developed malabsorption of fat (7 of 17, 41%) or xylose (8 of 14, 57%). When the gluten was pretreated with PEP, fat malabsorption was avoided in 5 of 7 and xylose malabsorption in 4 of 8 of these same patients.

Conclusions: A significant proportion of asymptomatic patients with celiac sprue have abnormal celiac antibodies and fat or carbohydrate malabsorption. Pretreatment of gluten with PEP avoided the development of fat or carbohydrate malabsorption in the majority of those patients who developed fat or carbohydrate malabsorption after a 2-week gluten challenge.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Celiac Disease / diet therapy
  • Celiac Disease / prevention & control*
  • Chymotrypsin / administration & dosage
  • Cross-Over Studies
  • Dietary Supplements*
  • Double-Blind Method
  • Female
  • Gastrointestinal Agents / administration & dosage
  • Glutens*
  • Humans
  • Male
  • Middle Aged
  • Pepsin A / administration & dosage
  • Prolyl Oligopeptidases
  • Serine Endopeptidases / administration & dosage*
  • Trypsin / administration & dosage


  • Gastrointestinal Agents
  • Glutens
  • Serine Endopeptidases
  • Chymotrypsin
  • PREPL protein, human
  • Prolyl Oligopeptidases
  • Trypsin
  • Pepsin A