文章：

微生物群：癌症治疗的关键协调者

Microbiota: a key orchestrator of cancer therapy

原文发布日期：2017-03-17

DOI: 10.1038/nrc.2017.13

类型: Review Article

开放获取: 否

要点：

1. The human microbiota is the ensemble of bacteria and other microorganisms that inhabit the epithelial barrier surfaces of the body. The microbiota affects physiological functions, particularly metabolism, neurological and cognitive functions, haematopoiesis, inflammation and immunity.
2. The microbiota and its larger host represent a metaorganism in which the crosstalk between microorganisms and host cells is necessary for health, survival and regulation of physiological functions at the local barrier level and systemically. Mostly because of its effects on metabolism, cellular proliferation, inflammation and immunity, the microbiota regulates cancer at the level of predisposing conditions, initiation, genetic instability, susceptibility to host immune response, progression, comorbidity and response to therapy.
3. The gut microbiota affects aspects of drug metabolism, pharmacokinetics, anticancer effect and toxicity. The rate of absorption and bioavailability of many oral drugs, including cancer therapies, depends on their exposure in the gut to both host and bacterial enzymes before entering the circulation.
4. The microbiota regulates the response to different types of cancer chemotherapy by affecting their mechanism of action and toxicity. The best characterized are oxaliplatin and cyclophosphamide; the anticancer activity of which is affected by the gut microbiota, which primes myeloid cells for production of reactive oxygen species in the case of oxaliplatin and facilitates the induction of an anticancer T cell response in the case of CTX.
5. The role of the microbiota in modulating the response to anticancer radiotherapy remains to be fully characterized. However, germ-free mice have been described as being less susceptible to the toxicity of radiation than conventionally raised mice, and evidence in humans and experimental animals suggests that the composition of the intestinal microbiota may affect the severity of radiation-induced mucosal toxicity.
6. The composition of the gut microbiota modulates both inflammation and adaptive immunity and thereby regulates the effectiveness of cancer immune therapies, such as adoptive T cell transfer preceded by total body irradiation, intratumoural treatment with CpG-oligodeoxynucleotides and immune checkpoint blockade with anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA4) and anti-programmed cell death protein 1 ligand 1 (PDL1).
7. Evidence of the important role of the microbiota in controlling cancer therapy effectiveness and toxicity is derived mainly from data in experimental animals, and translation of these findings to human clinical medicine remains challenging. Additional human data should be obtained and new technologies developed in order to safely target the microbiota to improve anticancer therapies while attenuating the toxic side effects.

要点翻译：

1. 人体微生物群是栖息于体表上皮屏障的细菌及其他微生物的集合体。微生物群影响着生理功能，特别是新陈代谢、神经与认知功能、造血作用、炎症及免疫应答。
2. 微生物群与其宿主共同构成一个超生物体，其中微生物与宿主细胞的交互对话对于健康、生存以及局部屏障和全身生理功能的调节至关重要。主要通过对代谢、细胞增殖、炎症和免疫的影响，微生物群在易感条件、起始阶段、遗传不稳定性、宿主免疫应答敏感性、进展过程、合并症及治疗反应等多个层面调控癌症发展。
3. 肠道微生物群影响药物代谢、药代动力学、抗癌效应及毒性反应。许多口服药物（包括癌症疗法）的吸收速率和生物利用度，取决于其在进入循环系统前接触肠道内宿主酶及细菌酶的程度。
4. 微生物群通过影响作用机制和毒性反应，调控对不同类型癌症化疗的应答。研究最充分的是奥沙利铂和环磷酰胺：前者依赖肠道微生物群激活髓系细胞产生活性氧，后者则通过肠道菌群促进抗癌T细胞应答的诱导。
5. 微生物群在调节抗癌放疗应答中的作用尚待全面阐明。然而，已有研究表明无菌小鼠比常规饲养小鼠对放射毒性更具抵抗力，人类及实验动物证据提示肠道菌群组成可能影响放射诱导黏膜毒性的严重程度。
6. 肠道菌群组成同时调节炎症反应与适应性免疫，从而影响癌症免疫疗法的效果，包括全身照射后的过继性T细胞移植、CpG寡脱氧核苷酸的瘤内治疗，以及抗CTLA4和抗PDL1免疫检查点阻断疗法。
7. 关于微生物群在控制癌症疗法效能与毒性中重要作用的相关证据，主要来源于实验动物数据，将这些发现转化应用于人类临床医学仍面临挑战。需要获取更多人类数据并开发新技术，以安全靶向微生物群，在增强抗癌疗效的同时减轻毒副作用。

英文摘要：

The microbiota is composed of commensal bacteria and other microorganisms that live on the epithelial barriers of the host. The commensal microbiota is important for the health and survival of the organism. Microbiota influences physiological functions from the maintenance of barrier homeostasis locally to the regulation of metabolism, haematopoiesis, inflammation, immunity and other functions systemically. The microbiota is also involved in the initiation, progression and dissemination of cancer both at epithelial barriers and in sterile tissues. Recently, it has become evident that microbiota, and particularly the gut microbiota, modulates the response to cancer therapy and susceptibility to toxic side effects. In this Review, we discuss the evidence for the ability of the microbiota to modulate chemotherapy, radiotherapy and immunotherapy with a focus on the microbial species involved, their mechanism of action and the possibility of targeting the microbiota to improve anticancer efficacy while preventing toxicity.

摘要翻译： 

微生物群由共生细菌及其他寄居于宿主上皮屏障的微生物组成。共生微生物群对机体的健康和生存至关重要，其影响从局部屏障稳态的维持到全身代谢、造血、炎症、免疫等生理功能的调节。微生物群还参与上皮屏障及无菌组织中癌症的发生、发展与转移。近年研究明确，微生物群尤其是肠道微生物群可调控癌症治疗效果并影响毒性副作用的易感性。本文综述了微生物群调节化疗、放疗及免疫治疗的证据，重点涉及相关菌株、作用机制，以及靶向微生物群以增强抗癌疗效并降低毒性的可能性。

原文链接：

Microbiota: a key orchestrator of cancer therapy