Ahmed Ishfaq, Umar Shahid
Department of Surgery and University of Kansas Cancer Center, University of Kansas Medical Center, Kansas City KS, USA.
Curr Colorectal Cancer Rep. 2018 Dec;14(6):217-225. doi: 10.1007/s11888-018-0416-7. Epub 2018 Oct 11.
The trillions of microbes collectively referred to as the human microbiota, inhabit the human body and establish a beneficial relationship with the host. It is clear however that dysbiosis impacting microbial diversity in the gut, may lead to development of inflammatory and malignant gastrointestinal diseases including colorectal cancer (CRC). We provide a literature review of the recent influx of information related to the alterations in gut microbiota composition that influences CRC incidence and progression.
A growing body of evidence implicates altered gut microbiota in the development of CRC. Profiles of CRC associated microbiota have been shown to differ from those in healthy subjects and bacterial phylotypes vary depending on the primary tumor location. The compositional variation in the microbial profile is not restricted to cancerous tissue however and is different between cancers of the proximal and distal colons, respectively. More recently, studies have shed light on the "driver-passenger" model for CRC wherein, driver bacteria cause inflammation, increased cell proliferation and production of genotoxic substances to contribute towards mutational acquisition associated with adenoma-carcinoma sequence. These changes facilitate gradual replacement of driver bacteria by passengers that either promote or suppress tumor progression. Significant advances have also been made in associating individual bacterial species to consensus molecular subtypes (CMS) of CRC and this remarkable development is expected to galvanize scientific community into advancing therapeutic strategies for CRC.
Increasing evidence suggests a link between the intestinal microbiota and CRC development although the mechanisms through which the bacterial constituents of the microbiome contribute towards CRC are complex and yet to be fully fathomed. Thus, more exhaustive and mechanistic studies are needed to identify key interactions amongst diet, microbial community and metabolites that help facilitate the adenoma-carcinoma sequence evolution in CRC. It is expected that development of therapeutics based on microbial association with CMS will likely facilitate the translation of molecular subtypes into the clinic for CRCs and potentially other malignancies.
数万亿微生物共同构成了人类微生物群，它们栖息在人体中，并与宿主建立了有益的关系。然而，很明显，影响肠道微生物多样性的生态失调可能会导致包括结直肠癌（CRC）在内的炎症性和恶性胃肠道疾病的发生。我们对最近大量涌现的有关肠道微生物群组成变化影响CRC发病率和进展的信息进行了文献综述。
越来越多的证据表明肠道微生物群的改变与CRC的发生有关。已显示CRC相关微生物群的特征与健康受试者不同，并且细菌系统型因原发性肿瘤位置而异。然而，微生物谱的组成变化不仅限于癌组织，分别在近端和远端结肠癌之间也有所不同。最近，研究揭示了CRC的“驱动-乘客”模型，其中驱动细菌会引起炎症、增加细胞增殖并产生遗传毒性物质，从而导致与腺瘤-癌序列相关的突变发生。这些变化促进了驱动细菌逐渐被促进或抑制肿瘤进展的乘客细菌所取代。在将个体细菌种类与CRC的共识分子亚型（CMS）相关联方面也取得了重大进展，这一显著进展有望促使科学界推进CRC的治疗策略。
越来越多的证据表明肠道微生物群与CRC的发生之间存在联系，尽管微生物组的细菌成分促成CRC的机制很复杂，尚未完全弄清楚。因此，需要更详尽和深入的机制研究来确定饮食、微生物群落和代谢产物之间的关键相互作用，这些相互作用有助于促进CRC中腺瘤-癌序列的演变。预计基于微生物与CMS关联的疗法的开发可能会促进分子亚型在CRC及其他潜在恶性肿瘤临床治疗中的应用。
