Bacterial enzymes used for colon-specific drug delivery are decreased in active Crohn's disease.
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.
Laboratoire de Biochimie, Faculté de Pharmacie, Lille, France.
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Carrette
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Favier
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Mizon
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Neut
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Cortot
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Colombel
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Mizon
D000328:Adult; D016022:Case-Control Studies; D003106:Colon / Q000201:enzymology* / Q000382:microbiology*; D003424:Crohn Disease / Q000188:drug therapy / Q000201:enzymology* / Q000382:microbiology; D005243:Feces / Q000201:enzymology; D005260:Female; D005966:Glucuronidase / Q000378:metabolism*; D006801:Humans; D008297:Male; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism*; D009601:Nitroreductases; D001616:beta-Galactosidase / Q000378:metabolism; D001617:beta-Glucosidase / Q000378:metabolism*
D009247:NADH, NADPH Oxidoreductases; D009601:Nitroreductases; C021106:azoreductase; D001617:beta-Glucosidase; D001616:beta-Galactosidase; D005966:Glucuronidase