Irinotecan (CPT-11) chemotherapy alters intestinal microbiota in tumour bearing rats.
Irinotecan (CPT-11) chemotherapy alters intestinal microbiota in tumour bearing rats.
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DOI：
10.1371/journal.pone.0039764
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Gänzle MG
中科院分区：
文献类型：
--
作者：
Lin XB;Dieleman LA;Ketabi A;Bibova I;Sawyer MB;Xue H;Field CJ;Baracos VE;Gänzle MG
肠道微生物区系介导伊立替康(CPT-11)癌症治疗的毒性，并在CPT-11导致屏障功能丧失后引起全身感染。因此，肠道微生物区系及其功能是减轻CPT-11毒性的潜在治疗目标。然而，CPT-11治疗期间的微生物区系变化仍然没有得到很好的描述。本研究分析了CPT-11化疗对肠道微生物区系的影响。定性和定量的分类分析和功能分析相结合，以描述基于CPT-11的化疗期间的肠道微生物区系，以及在有或没有口服谷氨酰胺的情况下，一种已知可以降低CPT-11毒性的治疗方法。在第一组实验中，荷瘤大鼠接受剂量密集型CPT-11方案(125mgkg−1×3d)，加或不加口服谷氨酰胺丸(0.75g kg−1)。在随后的更面向临床的化疗方案中，大鼠接受了两个周期的CPT-11(50 mg kg−1)和5-氟尿嘧啶(50 mg kg−1)。随着时间的推移，对粪便样本的分析表明，肿瘤改变了肠道微生物区系的组成，增加了旋毛虫I、XI和肠杆菌科细菌的丰度。CPT-11化疗增加了盲肠梭菌群XI和肠杆菌科细菌，尤其是在剂量强化治疗后。谷氨酰胺治疗防止了CPT-11给药后主要细菌群的丰度降低，即总细菌、梭状芽胞杆菌第VI群和类杆菌群。盲肠微生物区系中未检测到致病性大肠埃希菌和艰难梭菌的毒力因子/毒素基因。总而言之，结肠癌种植和基于CPT-11的化疗都破坏了肠道微生物区系。口服谷氨酰胺可部分减轻CPT-11的毒性，并引起肠道微生物区系的暂时性改变。
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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DOI：
10.1073/pnas.0901329106
发表时间：
2009-06-02
影响因子：
11.1
作者：
Critchley-Thorne, Rebecca J.;Simons, Diana L.;Lee, Peter P.
通讯作者：
Lee, Peter P.
影响因子：
30.3
作者：
Lupp, Claudia;Robertson, Marilyn L.;Finlay, B. Brett
通讯作者：
Finlay, B. Brett
影响因子：
9.8
作者：
Malinen, E;Rinttilä, T;Palva, A
通讯作者：
Palva, A
影响因子：
3
作者：
Kurita, Akinobu;Kado, Shoichi;Yokokura, Teruo
通讯作者：
Yokokura, Teruo
影响因子：
2.3
作者：
Dorofeyev, A. E.;Vasilenko, I. V.;Rassokhina, O. A.
通讯作者：
Rassokhina, O. A.