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

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 beta-glucuronidase produced by gut bacteria is thought to be involved. Results: Diarrhea occurred, as expected, following irinotecan treatment. beta-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 beta-glucuronidase producing) and decreases in Lactobacillus spp., Bifidobacterium spp. (both beneficial bacteria), and Bacteroides spp. (beta-glucuronidase producing, major component of intestinal flora). Methods: Rats were treated with 200 mg/kg irinotecan and killed at various time points up to 72 h. Rats were monitored for diarrhea. Sections were stained for beta-glucuronidase expression, and faecal DNA was analysed using real time PCR. Conclusions: Irinotecan-induced diarrhea may be caused by an increase in beta-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.