微生物菌群与抗肿瘤药物疗效及不良反应相关性研究进展

王娜; 韩晓红

doi:10.12290/xhyxzz.2023-0212

微生物菌群与抗肿瘤药物疗效及不良反应相关性研究进展

doi: 10.12290/xhyxzz.2023-0212

王娜^{1, 2},
韩晓红^{1, 2, ,}

1.
中国医学科学院北京协和医院临床药理研究中心国家药监局药物临床研究与评价重点实验室创新药物临床PK/PD北京市重点实验室，北京 100730
2.
中国医学科学院北京协和医院疑难重症及罕见病国家重点实验室，北京 100730

基金项目:

中央高水平医院临床科研专项 2022-PUMCH-B-033

详细信息

通讯作者:
韩晓红, E-mail: hanxiaohong@pumch.cn

中图分类号: R73;R453;R456
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出版历程
- 收稿日期: 2023-04-26
- 录用日期: 2023-06-15
- 网络出版日期: 2023-07-05
- 刊出日期: 2023-09-30

Research Progress on the Correlation Between Microbiota and the Efficacy and Adverse Reactions of Antitumor Drug

WANG Na^{1, 2},
HAN Xiaohong^{1, 2
, ,}

1.
Clinical Pharmacology Research Center, NMPA Key Laboratory for Clinical Research and Evaluation of Drug, Beijing Key Laboratory of Clinical PK & PD Investigation for Innovative Drugs, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China
2.
State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China

Funds:

National High Level Hospital Clinical Research Funding 2022-PUMCH-B-033

More Information

Corresponding author: HAN Xiaohong, E-mail: hanxiaohong@pumch.cn

摘要

摘要: 抗肿瘤药物不断推陈出新，但药物响应率有限及药物不良反应问题严重限制了其临床应用。近年来，“药物微生物组学”概念兴起，越来越多的研究表明，人体微生物菌群在抗肿瘤药物治疗中发挥重要作用。本文从化疗药物、分子靶向药物、免疫治疗药物三方面综述微生物菌群与抗肿瘤药物的相互作用，机制涉及免疫调节、激素水平调节、代谢物水平调节、药物生物转化及跨膜转运调节等，并对可改善抗肿瘤药物疗效及不良反应的微生物菌群调控策略进行概述，以期为临床抗肿瘤药物个体化治疗提供参考。
- 药物微生物组学 /
- 微生物菌群 /
- 抗肿瘤药物 /
- 药物疗效 /
- 药物不良反应
Abstract: Despite the rapid development of antitumor drugs, the limited drug response rate and adverse drug reactions have severely limited their clinical application. In recent years, the concept of "pharmacomicrobiomics" has emerged, and more and more studies have shown thatmicrobiota plays an important role in the treatment of antitumor drugs. Herein, the interaction between microbiota and antitumor drugs is reviewed from the aspects of chemotherapeutics, molecular targeted drugs and immunotherapy drugs. The mechanism involves immune regulation, hormone regulation, metabolite regulation, drug biotransformation and transmembrane transport regulation. The microbiota regulation strategies that can improve the efficacy and reduce adverse reactions of antitumor drugs are reviewed, in order to provide reference for the individualized treatment of clinical antitumor drugs.
- pharmacomicrobiomics /
- microbiota /
- antitumor drugs /
- drug efficacy /
- adverse drug reactions
注释:

作者贡献：王娜负责文献检索、论文撰写；韩晓红负责选题设计、论文审校。

利益冲突：所有作者均声明不存在利益冲突

HTML全文

表 1 微生物菌群对化疗药物疗效及不良反应的影响及其作用机制

机制分类	微生物菌群	化疗药物	微生物菌群影响药物疗效及不良反应
免疫调节	约氏乳杆菌、海氏肠球菌	环磷酰胺	增加肿瘤内细胞毒性T细胞/调节性T细胞比例，增强疗效
	肠道巴恩斯氏菌	环磷酰胺	促进γδT细胞肿瘤浸润，增强疗效
	粪球菌属、Dorea及瘤胃球菌属	环磷酰胺、顺铂、卡铂	诱导CD4⁺ T细胞水平升高，增强疗效
	具核梭杆菌	奥沙利铂、5-Fu	激活TLR4-MYD88-NF-κB通路，导致机体耐药
	大肠杆菌、嗜黏蛋白阿克曼菌等	吉西他滨、5-Fu、伊立替康、奥沙利铂	激活NF-κB信号通路，导致黏膜炎不良反应
	鼠李糖乳酸杆菌	5-Fu、奥沙利铂	恢复厚壁菌门/拟杆菌门丰度比，缓解黏膜炎不良反应
激素水平调节	大肠杆菌	5-Fu	降低宿主糖皮质激素水平, 加剧黏膜炎不良反应
	瘤胃球菌属、拟杆菌属	比卡鲁胺、恩杂鲁胺、阿比特龙	将雄激素前体转化为活性雄激素，降低雄激素剥夺疗法疗效
代谢水平调节	丁酸盐产生菌	5-Fu、吉西他滨、奥沙利铂	促进肿瘤细胞凋亡，增强疗效
	丁酸梭状芽孢杆菌	顺铂、吉西他滨	上调丁酸盐产生菌丰度，缓解肠道黏膜炎不良反应
药物生物转化及跨膜转运调节	大肠杆菌	5-Fu	通过核糖核苷酸代谢途径及细菌维生素B6和B9作用，增强疗效
	β-葡萄糖醛酸酶产生菌	伊立替康	将SN-38G代谢为SN-38，导致肠道损伤不良反应
	-	5-Fu	引起索利夫定与5-Fu间药物相互作用，导致严重不良反应
	植生拉乌尔菌、肺炎克雷伯菌、大肠杆菌	多柔比星	促进药物代谢，减少不良反应
	假单胞菌	甲氨蝶呤	产生羧肽酶G2促进药物代谢，减少不良反应
TLR4：Toll样受体4；MYD88：髓样分化因子88; NF-κB：核因子κB; 5-Fu：5-氟尿嘧啶；SN-38G：SN-38葡萄糖醛酸苷；SN-38：7-乙基-10-羟基喜树碱

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微生物菌群与抗肿瘤药物疗效及不良反应相关性研究进展

doi: 10.12290/xhyxzz.2023-0212

通讯作者:
韩晓红, E-mail: hanxiaohong@pumch.cn

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Research Progress on the Correlation Between Microbiota and the Efficacy and Adverse Reactions of Antitumor Drug

Corresponding author: HAN Xiaohong, E-mail: hanxiaohong@pumch.cn

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微生物菌群与抗肿瘤药物疗效及不良反应相关性研究进展

doi: 10.12290/xhyxzz.2023-0212

通讯作者: 韩晓红, E-mail: hanxiaohong@pumch.cn

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Research Progress on the Correlation Between Microbiota and the Efficacy and Adverse Reactions of Antitumor Drug

Corresponding author: HAN Xiaohong, E-mail: hanxiaohong@pumch.cn

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通讯作者:
韩晓红, E-mail: hanxiaohong@pumch.cn