Bacterial enzymes used for colon-specific drug delivery are decreased in active Crohn's disease

Dig Dis Sci. 1995 Dec;40(12):2641-6. doi: 10.1007/BF02220454.

Abstract

Enzymes produced by colonic microflora have been proposed for triggering local delivery of antiinflammatory azo-bond drugs and prodrugs to the colon. This approach could be advantageous in steroid treatment of inflammatory bowel diseases, thus sparing steroids' side effects. We recently demonstrated that the metabolic activity of digestive flora, assessed on the activity of fecal glycosidases, was decreased in patients with active Crohn's disease. In the present study, the azoreductase activity in feces of 14 patients with active Crohn's disease was decreased (11.39 +/- 7.93 mU/g F) as compared with 12 healthy subjects (51.13 +/- 21.39 mU/g F). beta-D-Glucosidase and beta-D-glucuronidase activities in fecal homogenates incubated under anaerobic conditions were also decreased in patients. These data bring into question the therapeutic usefulness for those patients of azo-bond drugs and glycoside prodrugs. They could explain the therapeutic failure of some of those drugs in active ileocolic and colic Crohn's disease.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Case-Control Studies
  • Colon / enzymology*
  • Colon / microbiology*
  • Crohn Disease / drug therapy
  • Crohn Disease / enzymology*
  • Crohn Disease / microbiology
  • Feces / enzymology
  • Female
  • Glucuronidase / metabolism*
  • Humans
  • Male
  • NADH, NADPH Oxidoreductases / metabolism*
  • beta-Galactosidase / metabolism
  • beta-Glucosidase / metabolism*

Substances

  • NADH, NADPH Oxidoreductases
  • azoreductase
  • beta-Glucosidase
  • beta-Galactosidase
  • Glucuronidase