Virulence genes are a signature of the microbiome in the colorectal tumor microenvironment.
Virulence genes are a signature of the microbiome in the colorectal tumor microenvironment.
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DOI：
10.1186/s13073-015-0177-8
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发表时间：
2015
期刊：
影响因子：
12.3
通讯作者：
Blekhman R
中科院分区：
文献类型：
--
作者：
Burns MB;Lynch J;Starr TK;Knights D;Blekhman R
人类肠道微生物组与结肠癌的发展有关，最近的研究发现，与健康对照组相比，癌症患者的微生物组发生了变化。研究肿瘤微环境中的微生物群落可能会揭示宿主-细菌相互作用在结直肠癌中的作用。在这里，我们强调了结直肠肿瘤微生物组相对于来自同一个体的匹配正常结肠组织的主要变化，使我们能够调查肿瘤微环境中的微生物群落，并为环境和宿主遗传对微生物组的影响提供内在控制。我们对44个原发性肿瘤和44个患者匹配的正常结肠组织样本中的微生物组进行了测序，以确定差异丰富的微生物分类群。这些数据还用于功能性表征癌症和正常样本对的微生物组，并鉴定肿瘤相关微生物群中富集的功能途径。我们发现，与附近的健康组织相比，肿瘤含有不同的微生物群落。我们的研究结果表明，肿瘤微环境中的微生物多样性增加，其中包括梭杆菌属和普罗威登斯菌属在内的嗜酸性和致病性细菌类群的丰度发生变化。虽然梭杆菌先前与结直肠癌有关，但普罗维登西亚是一种新的肿瘤相关药物，在先前的研究中尚未发现。此外，我们确定了一个明确的，显着的富集预测毒力相关基因在结直肠癌微环境中，可能依赖于梭杆菌和普罗维登西亚的基因组。这项工作确定了与结直肠癌显著相关的细菌分类群，包括肿瘤微环境中普罗维登西亚丰度升高的新发现。我们还描述了肿瘤相关微生物组中差异存在的预测代谢途径和酶，并显示了肿瘤微环境中毒力相关细菌基因的富集。这种预测的毒力富集支持了微生物组在结直肠癌发展和/或进展中起积极作用的假设。我们的研究结果为未来的预后和治疗研究提供了一个起点，有可能改善患者的预后。本文的在线版本（doi：10.1186/s13073-015-0177-8）包含补充材料，可供授权用户使用。
The human gut microbiome is associated with the development of colon cancer, and recent studies have found changes in the microbiome in cancer patients compared to healthy controls. Studying the microbial communities in the tumor microenvironment may shed light on the role of host–bacteria interactions in colorectal cancer. Here, we highlight the major shifts in the colorectal tumor microbiome relative to that of matched normal colon tissue from the same individual, allowing us to survey the microbial communities in the tumor microenvironment and providing intrinsic control for environmental and host genetic effects on the microbiome. We sequenced the microbiome in 44 primary tumor and 44 patient-matched normal colon tissue samples to determine differentially abundant microbial taxa These data were also used to functionally characterize the microbiome of the cancer and normal sample pairs and identify functional pathways enriched in the tumor-associated microbiota. We find that tumors harbor distinct microbial communities compared to nearby healthy tissue. Our results show increased microbial diversity in the tumor microenvironment, with changes in the abundances of commensal and pathogenic bacterial taxa, including Fusobacterium and Providencia. While Fusobacterium has previously been implicated in colorectal cancer, Providencia is a novel tumor-associated agent which has not been identified in previous studies. Additionally, we identified a clear, significant enrichment of predicted virulence-associated genes in the colorectal cancer microenvironment, likely dependent upon the genomes of Fusobacterium and Providencia. This work identifies bacterial taxa significantly correlated with colorectal cancer, including a novel finding of an elevated abundance of Providencia in the tumor microenvironment. We also describe the predicted metabolic pathways and enzymes differentially present in the tumor-associated microbiome, and show an enrichment of virulence-associated bacterial genes in the tumor microenvironment. This predicted virulence enrichment supports the hypothesis that the microbiome plays an active role in colorectal cancer development and/or progression. Our results provide a starting point for future prognostic and therapeutic research with the potential to improve patient outcomes. The online version of this article (doi:10.1186/s13073-015-0177-8) contains supplementary material, which is available to authorized users.
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影响因子：
3.7
作者：
Chen W;Liu F;Ling Z;Tong X;Xiang C
通讯作者：
Xiang C
人类结直肠癌微生物组的多样化模式
影响因子：
4.2
作者：
Geng J;Fan H;Tang X;Zhai H;Zhang Z
通讯作者：
Zhang Z
影响因子：
3.1
作者：
ALBERT, MJ;ALAM, K;MATHAN, MM
通讯作者：
MATHAN, MM
影响因子：
11.5
作者：
Bonnet, Mathilde;Buc, Emmanuel;Darfeuille-Michaud, Arlette
通讯作者：
Darfeuille-Michaud, Arlette
影响因子：
7
作者：
Castellarin, Mauro;Warren, Rene L.;Holt, Robert A.
通讯作者：
Holt, Robert A.