Deficient UDP‐glucuronosyltransferase detoxification enzyme activity in the small intestinal mucosa of patients with coeliac disease

Abstract

Small intestinal malignancies in humans are rare; however, patients with coeliac disease have a relatively high risk for such tumours. Intestinal UDP-glucuronosyltransferases are phase II drug metabolism enzymes also involved in the detoxification of ingested toxins and carcinogens. As many toxins and carcinogens are ingested via food, the human gastrointestinal tract not only has an important role in the uptake of essential nutrients, but also acts as a first barrier against such harmful constituents of the food. Therefore, the gastrointestinal mucosa contains high levels of detoxification enzymes such as cytochromes-P450, glutathione S-transferases and UDP-glucuronosyltransferases. To compare the UDP-glucuronosyltransferase detoxification capacity in small intestinal mucosa of patients with coeliac disease vs. that in normal controls. We assessed UDP-glucuronosyltransferase enzyme activities towards 4-methylumbelliferone in small intestinal biopsies of patients with coeliac disease (n = 22) and age- and sex-matched controls (n = 27). Small intestinal UDP-glucuronosyltransferase enzyme activity in controls was significantly higher than in patients with coeliac disease: 0.55 +/- 0.27 vs. 0.35 +/- 0.16 nmol/min mg protein, respectively (mean +/- s.d., P = 0.005). The low small intestinal UDP-glucuronosyltransferase detoxification activity in patients with coeliac disease may result in a deficient detoxification of potential carcinogens, and thus could explain in part the relatively high small intestinal cancer risk in these patients.