Effects of Docetaxel Injection and Docetaxel Micelles on the Intestinal Barrier and Intestinal Microbiota.
Effects of Docetaxel Injection and Docetaxel Micelles on the Intestinal Barrier and Intestinal Microbiota.
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多西他赛注射液和多西他赛胶束对肠道屏障和肠道菌群的影响
DOI：
10.1002/advs.202102952
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发表时间：
2021-12
期刊：
影响因子：
--
通讯作者：
Qian Z
中科院分区：
文献类型：
--
作者：
Liu Q;Lu Y;Xiao Y;Yuan L;Hu D;Hao Y;Han R;Peng J;Qian Z
越来越多的证据表明，化疗药物影响肠道屏障的完整性，改变肠道微生物群，从而限制了癌症化疗的治疗效果。多西他赛（DTX）用于乳腺癌治疗，具有胃肠道副作用，但DTX制剂对肠道屏障和肠道微生物群的影响仍然未知。因此，在这项工作中，研究了DTX注射液（游离DTX，商业制剂）和DTX/甲氧基聚（乙二醇）-嵌段-聚（D，L-丙交酯）（mPEG-PDLLA）（DTX胶束，纳米制剂）对肠道屏障和肠道微生物群完整性的影响。结果发现，游离的DTX比DTX胶束引起更大的肠屏障损伤。DTX胶束处理组中肠道微生物群的多样性以及嗜粘蛋白阿克曼氏菌和活泼瘤胃球菌的相对丰度显著高于游离DTX处理组。此外，在抗生素混合物预处理的小鼠中，肿瘤生长速率升高，表明肠道微生物群的多样性和组成可能与肿瘤进展相关。这项工作表明，不同的化疗药物制剂对肠道屏障和肠道微生物群的完整性具有不同的影响。
Increasing evidence has suggested that chemotherapeutics affect the integrity of the intestinal barrier and alter the intestinal microbiota, thus limiting the therapeutic outcomes of cancer chemotherapy. Docetaxel (DTX) is used for breast cancer treatment and has gastrointestinal side effects, but the influence of DTX formulations on the intestinal barrier and intestinal microbiota remains unknown. Therefore, in this work, the influence of DTX injection (free DTX, commercial formulation) and DTX/methoxy poly(ethylene glycol)‐block‐poly(D,L‐lactide) (mPEG‐PDLLA) (DTX micelles, nanoformulation) on the integrity of the intestinal barrier and the intestinal microbiota is investigated. It is found that the free DTX causes significantly greater intestinal barrier damage than the DTX micelles. The diversity of the intestinal microbiota, and the relative abundance of Akkermansia muciniphila and Ruminococcus gnavus in the DTX micelle‐treated group is significantly higher than that in the free DTX‐treated group. Moreover, the tumor growth rate is elevated in antibiotic mixture‐pretreated mice, demonstrating that the diversity and composition of the intestinal microbiota may be associated with tumor progression. This work demonstrates that different formulations of chemotherapeutics have different effects on the integrity of the intestinal barrier and the intestinal microbiota.