Faecal microflora and β-glucuronidase expression are altered in an irinotecan-induced diarrhea model in rats

Abstract

Objectives: Chemotherapy-induced diarrhea (CID) is a well recognized side effect of cancer treatment. However, the pathophysiology behind this debilitating side effect remains unclear. Irinotecan causes cholinergic and delayed onset diarrhea in patients, in which β-glucuronidase produced by gut bacteria is thought to be involved. Methods: Rats were treated with 200mg/kg irinotecan and killed at various time points up to 72 h. Rats were monitored for diarrhea. Sections were stained for β-glucuronidase expression, and faecal DNA was analysed using real time PCR. Results: Diarrhea occurred, as expected, following irinotecan treatment. β-glucuronidase expression increased in the jejunum and colon. Faecal flora changed quantitatively after treatment also, with increases in E. coli, Staphylococcus spp., and Clostridium spp. (all β-glucuronidase producing), and decreases in Lactobacillus spp., Bifidobacterium spp. (both beneficial bacteria), and Bacteroides spp. (β-glucuronidase producing, major component of intestinal flora). Conclusions: Irinotecan-induced diarrhea may be caused by an increase in β-glucuronidase producing bacteria. However, the increase in bacteria may also be caused by irinotecan, further exaggerating the toxicity of the drug, and emphasising the need for these specific bacteria to be therapeutically targeted for successful treatment regimens to be accomplished.