Irinotecan (CPT-11) chemotherapy alters intestinal microbiota in tumour bearing rats

PLoS One. 2012;7(7):e39764. doi: 10.1371/journal.pone.0039764. Epub 2012 Jul 26.


Intestinal microbiota mediate toxicity of irinotecan (CPT-11) cancer therapies and cause systemic infection after CPT-11-induced loss of barrier function. The intestinal microbiota and their functions are thus potential targets for treatment to mitigate CPT-11 toxicity. However, microbiota changes during CPT-11 therapy remain poorly described. This study analysed changes in intestinal microbiota induced by CPT-11 chemotherapy. Qualitative and quantitative taxonomic analyses, and functional analyses were combined to characterize intestinal microbiota during CPT-11-based chemotherapy, and in presence or absence of oral glutamine, a treatment known to reduce CPT-11 toxicity. In the first set of experiments tumour-bearing rats received a dose-intensive CPT-11 regimen (125 mg kg(-1)×3 days), with or without oral glutamine bolus (0.75 g kg(-1)). In a subsequent more clinically-oriented chemotherapy regimen, rats received two cycles of CPT-11 (50 mg kg(-1)) followed by 5-flurouracil (50 mg kg(-1)). The analysis of fecal samples over time demonstrated that tumours changed the composition of intestinal microbiota, increasing the abundance of clostrridial clusters I, XI, and Enterobacteriaceae. CPT-11 chemotherapy increased cecal Clostridium cluster XI and Enterobacteriaceae, particularly after the dose-intensive therapy. Glutamine treatment prevented the reduced abundance of major bacterial groups after CPT-11 administration; i.e. total bacteria, Clostridium cluster VI, and the Bacteroides-group. Virulence factor/toxin genes of pathogenic Escherichia coli and Clostridium difficile were not detected in the cecal microbiota. In conclusion, both colon cancer implantation and CPT-11-based chemotherapies disrupted the intestinal microbiota. Oral glutamine partially mitigated CPT-11 toxicity and induced temporary changes of the intestinal microbiota.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / adverse effects*
  • Antineoplastic Agents / therapeutic use
  • Camptothecin / adverse effects
  • Camptothecin / analogs & derivatives*
  • Camptothecin / therapeutic use
  • Cecum / drug effects
  • Cecum / microbiology
  • Cell Transformation, Neoplastic
  • Dose-Response Relationship, Drug
  • Feces / microbiology
  • Female
  • Intestines / drug effects*
  • Intestines / microbiology*
  • Irinotecan
  • Metagenome / drug effects*
  • Neoplasms / drug therapy*
  • Neoplasms / microbiology*
  • Neoplasms / pathology
  • Rats


  • Antineoplastic Agents
  • Irinotecan
  • Camptothecin