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微生物群与结直肠癌:从肠道到床边

Microbiota and Colorectal Cancer: From Gut to Bedside.

作者信息

Silva Miguel, Brunner Valentina, Tschurtschenthaler Markus

机构信息

Institute of Molecular Oncology and Functional Genomics, Center for Translational Cancer Research (TranslaTUM), Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany.

Graduate Program in Areas of Basic and Applied Biology (GABBA)/ICBAS - Institute for the Biomedical Sciences Abel Salazar, Porto University, Porto, Portugal.

出版信息

Front Pharmacol. 2021 Sep 30;12:760280. doi: 10.3389/fphar.2021.760280. eCollection 2021.

Abstract

Colorectal cancer (CRC) is a complex condition with heterogeneous aetiology, caused by a combination of various environmental, genetic, and epigenetic factors. The presence of a homeostatic gut microbiota is critical to maintaining host homeostasis and determines the delicate boundary between health and disease. The gut microbiota has been identified as a key environmental player in the pathogenesis of CRC. Perturbations of the gut microbiota structure (loss of equilibrium and homeostasis) are associated with several intestinal diseases including cancer. Such dysbiosis encompasses the loss of beneficial microorganisms, outgrowth of pathogens and pathobionts and a general loss of local microbiota diversity and richness. Notably, several mechanisms have recently been identified how bacteria induce cellular transformation and promote tumour progression. In particular, the formation of biofilms, the production of toxic metabolites or the secretion of genotoxins that lead to DNA damage in intestinal epithelial cells are newly discovered processes by which the microbiota can initiate tumour formation. The gut microbiota has also been implicated in the metabolism of therapeutic drugs (conventional chemotherapy) as well as in the modulation of radiotherapy responses and targeted immunotherapy. These new findings suggest that the efficacy of a given therapy depends on the composition of the host's gut microbiota and may therefore vary from patient to patient. In this review we discuss the role of host-microbiota interactions in cancer with a focus on CRC pathogenesis. Additionally, we show how gut bacteria can be exploited in current therapies and how mechanisms directed by microbiota, such as immune cell boost, probiotics and oncolytic bacteria, can be applied in the development of novel therapies.

摘要

结直肠癌(CRC)是一种病因复杂的疾病,由多种环境、遗传和表观遗传因素共同作用引起。肠道微生物群的稳态对于维持宿主的内环境稳定至关重要,并决定了健康与疾病之间的微妙界限。肠道微生物群已被确定为CRC发病机制中的关键环境因素。肠道微生物群结构的扰动(平衡和稳态的丧失)与包括癌症在内的几种肠道疾病有关。这种生态失调包括有益微生物的丧失、病原体和致病共生菌的过度生长以及局部微生物群多样性和丰富度的普遍丧失。值得注意的是,最近已经确定了几种细菌诱导细胞转化和促进肿瘤进展的机制。特别是,生物膜的形成、有毒代谢产物的产生或导致肠道上皮细胞DNA损伤的基因毒素的分泌是微生物群引发肿瘤形成的新发现过程。肠道微生物群还与治疗药物(传统化疗)的代谢以及放疗反应和靶向免疫治疗的调节有关。这些新发现表明,特定治疗的疗效取决于宿主肠道微生物群的组成,因此可能因患者而异。在这篇综述中,我们讨论了宿主-微生物群相互作用在癌症中的作用,重点是CRC的发病机制。此外,我们展示了肠道细菌如何在当前治疗中得到利用,以及微生物群指导的机制,如免疫细胞增强、益生菌和溶瘤细菌,如何应用于新疗法的开发。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c65/8514721/deaa23f06a51/fphar-12-760280-g001.jpg

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