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Irinotecan (CPT-11) chemotherapy alters intestinal microbiota in tumour bearing rats Open Access
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Dieleman, Levinus A.
Sawyer, Michael B.
Field, Catherine J.
Baracos, Vickie E.
Gänzle, Michael G.
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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.
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Lin, X., Dieleman, L. A., Ketabi, A., Bibova, I., Sawyer, M. B., Xue, H., Field, C. J., Baracos, V. E., & Gänzle, M. G. (2012). Irinotecan (CPT-11) chemotherapy alters intestinal microbiota in tumour bearing rats. PLoS ONE, 7(7), e39764 [8 pages]. http://dx.doi.org/10.1371/journal.pone.0039764
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