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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微生物群的影响。

Effects of Docetaxel Injection and Docetaxel Micelles on the Intestinal Barrier and Intestinal Microbiota.

机构信息

State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, Sichuan, 610041, P. R. China.

West China School of Pharmacy, Sichuan University, Chengdu, 610041, P. R. China.

出版信息

Adv Sci (Weinh). 2021 Dec;8(24):e2102952. doi: 10.1002/advs.202102952. Epub 2021 Oct 28.

DOI:10.1002/advs.202102952
PMID:34713626
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8693036/
Abstract

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.

摘要

越来越多的证据表明，化疗药物会影响肠道屏障的完整性并改变肠道微生物群，从而限制癌症化疗的治疗效果。多西紫杉醇（DTX）用于乳腺癌治疗，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尚不清楚。因此，在这项工作中，研究了多西紫杉醇注射液（游离 DTX，商业制剂）和多西紫杉醇/甲氧基聚乙二醇-嵌段-聚（D，L-丙交酯）（mPEG-PDLLA）（DTX 胶束，纳米制剂）对肠道屏障完整性和肠道微生物群的影响。结果发现，游离 DTX 引起的肠道屏障损伤明显大于 DTX 胶束。DTX 胶束处理组的肠道微生物群多样性以及阿克曼氏菌和瘤胃球菌的相对丰度明显高于游离 DTX 处理组。此外，抗生素混合物预处理小鼠的肿瘤生长速度升高，表明肠道微生物群的多样性和组成可能与肿瘤进展有关。这项工作表明，不同的化疗药物制剂对肠道屏障的完整性和肠道微生物群有不同的影响。

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