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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.

Irinotecan (CPT-11) Chemotherapy Alters Intestinal Microbiota in Tumour Bearing Rats