title: Irinotecan (CPT-11) chemotherapy alters intestinal microbiota in tumour bearing rats.
abstract: 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.
authors: Department of Agriculture, Food and Nutritional Science, University of Alberta, Edmonton, Alberta, Canada.
authors: Xiaoxi B
authors: XB
authors: Lin
authors: Levinus A
authors: LA
authors: Dieleman
authors: Ali
authors: A
authors: Ketabi
authors: Ilona
authors: I
authors: Bibova
authors: Michael B
authors: MB
authors: Sawyer
authors: Hongyu
authors: H
authors: Xue
authors: Catherine J
authors: CJ
authors: Field
authors: Vickie E
authors: VE
authors: Baracos
authors: Michael G
authors: MG
authors: Gänzle
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D002166:Camptothecin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D002432:Cecum / Q000187:drug effects / Q000382:microbiology; D002471:Cell Transformation, Neoplastic; D004305:Dose-Response Relationship, Drug; D005243:Feces / Q000382:microbiology; D005260:Female; D007422:Intestines / Q000187:drug effects* / Q000382:microbiology*; D000077146:Irinotecan; D054892:Metagenome / Q000187:drug effects*; D009369:Neoplasms / Q000188:drug therapy* / Q000382:microbiology* / Q000473:pathology; D051381:Rats
chemical_list: D000970:Antineoplastic Agents; D000077146:Irinotecan; D002166:Camptothecin