Impaired inactivation of digestive proteases by deconjugated bilirubin: the possible mechanism for inflammatory bowel disease

Med Hypotheses. 2002 Aug;59(2):159-63. doi: 10.1016/s0306-9877(02)00243-8.


Inflammatory bowel disease refers to ulcerative colitis and Crohn's disease, two gut diseases with unknown causes. The dramatic increase in the last half century and the big difference in incidence for people with the same ethnic background but living in different areas strongly suggested that environmental factors played the dominant role for these diseases. The similarity in many aspects for these two diseases suggested a common causative factor. Here I suggest the impaired inactivation of digestive proteases by deconjugated bilirubin, as the result of the inhibition of bilirubin deconjugation enzyme, beta-glucuronidase, originated from the luminal bacteria and mucosa of the gut, to be a possible mechanism for both ulcerative colitis and Crohn's diseases. I also provide evidence to suggest that saccharin could be the causative or one of the most important risk factors for inflammatory bowel disease as for its inhibition on beta-glucuronidase in the intestine.

MeSH terms

  • Bilirubin / metabolism*
  • Digestive System / enzymology*
  • Endopeptidases / metabolism*
  • Humans
  • Inflammatory Bowel Diseases / enzymology
  • Inflammatory Bowel Diseases / etiology*
  • Protease Inhibitors / pharmacology*
  • Risk Factors
  • Saccharin / adverse effects


  • Protease Inhibitors
  • Endopeptidases
  • Saccharin
  • Bilirubin