The MOE Key Laboratory of Standardization of Chinese Medicines, Shanghai Key Laboratory of Compound Chinese Medicines, and the SATCM Key Laboratory of New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine (SHUTCM), Shanghai, China.
Front Cell Infect Microbiol. 2021 Oct 14;11:710945. doi: 10.3389/fcimb.2021.710945. eCollection 2021.
Irinotecan (CPT11) and its active metabolite ethyl-10-hydroxy-camptothecin (SN38) are broad-spectrum cytotoxic anticancer agents. Both cause cell death in rapidly dividing cells (e.g., cancer cells, epithelial cells, hematopoietic cells) and commensal bacteria. Therefore, CPT11 can induce a series of toxic side-effects, of which the most conspicuous is gastrointestinal toxicity (nausea, vomiting, diarrhea). Studies have shown that the gut microbiota modulates the host response to chemotherapeutic drugs. Targeting the gut microbiota influences the efficacy and toxicity of CPT11 chemotherapy through three key mechanisms: microbial ecocline, catalysis of microbial enzymes, and immunoregulation. This review summarizes and explores how the gut microbiota participates in CPT11 metabolism and mediates host immune dynamics to affect the toxicity and efficacy of CPT11 chemotherapy, thus introducing a new concept that is called "microbiota-host-irinotecan axis". Also, we emphasize the utilization of bacterial β-glucuronidase-specific inhibitor, dietary interventions, probiotics and strain-engineered interventions as emergent microbiota-targeting strategies for the purpose of improving CPT11 chemotherapy efficiency and alleviating toxicity.
伊立替康（CPT11）及其活性代谢物乙基-10-羟基喜树碱（SN38）是广谱细胞毒性抗癌药物。两者都会导致快速分裂的细胞（例如癌细胞、上皮细胞、造血细胞）和共生细菌死亡。因此，CPT11 可引起一系列毒性副作用，其中最明显的是胃肠道毒性（恶心、呕吐、腹泻）。研究表明，肠道微生物群调节宿主对化疗药物的反应。通过三种关键机制靶向肠道微生物群可以影响 CPT11 化疗的疗效和毒性：微生物生态变化、微生物酶的催化作用和免疫调节。这篇综述总结并探讨了肠道微生物群如何参与 CPT11 代谢并介导宿主免疫动态，从而影响 CPT11 化疗的毒性和疗效，从而引入了一个新概念，称为“微生物群-宿主-伊立替康轴”。此外，我们强调利用细菌β-葡萄糖醛酸酶特异性抑制剂、饮食干预、益生菌和经过工程改造的菌株干预作为新兴的微生物群靶向策略，以提高 CPT11 化疗的效率并减轻毒性。
