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Genomic and functional characterization of a mucosal symbiont involved in early-stage colorectal cancer
Cell Host & Microbe ( IF 20.6 ) Pub Date : 2021-09-17 , DOI: 10.1016/j.chom.2021.08.013
Melissa C Kordahi 1 , Ian B Stanaway 2 , Marion Avril 3 , Denise Chac 1 , Marie-Pierre Blanc 3 , Benjamin Ross 4 , Christian Diener 5 , Sumita Jain 6 , Paul McCleary 2 , Ana Parker 2 , Vincent Friedman 2 , Jennifer Huang 7 , Wynn Burke 7 , Sean M Gibbons 8 , Amy D Willis 9 , Richard P Darveau 6 , William M Grady 10 , Cynthia W Ko 3 , R William DePaolo 11
Affiliation  

Colorectal cancer is a major health concern worldwide. Growing evidence for the role of the gut microbiota in the initiation of CRC has sparked interest in approaches that target these microorganisms. However, little is known about the composition and role of the microbiota associated with precancerous polyps. Here, we found distinct microbial signatures between patients with and without polyps and between polyp subtypes using sequencing and culturing techniques. We found a correlation between Bacteroides fragilis recovered and the level of inflammatory cytokines in the mucosa adjacent to the polyp. Additional analysis revealed that B. fragilis from patients with polyps are bft-negative, activate NF-κB through Toll-like receptor 4, induce a pro-inflammatory response, and are enriched in genes associated with LPS biosynthesis. This study provides fundamental insight into the microbial microenvironment of the pre-neoplastic polyp by highlighting strain-specific genomic and proteomic differences, as well as more broad compositional differences in the microbiome.



中文翻译:

参与早期结直肠癌的黏膜共生体的基因组和功能表征

结直肠癌是世界范围内的主要健康问题。越来越多的证据表明肠道微生物群在 CRC 发病中的作用引发了人们对针对这些微生物的方法的兴趣。然而,关于与癌前息肉相关的微生物群的组成和作用知之甚少。在这里,我们使用测序和培养技术在有和没有息肉的患者之间以及息肉亚型之间发现了不同的微生物特征。我们发现恢复的脆弱拟杆菌与息肉附近粘膜中炎性细胞因子水平之间存在相关性。附加分析显示,来自息肉患者的脆弱拟杆菌是bft-阴性,通过 Toll 样受体 4 激活 NF-κB,诱导促炎反应,并富含与 LPS 生物合成相关的基因。这项研究通过突出菌株特异性基因组和蛋白质组学差异以及微生物组中更广泛的组成差异,提供了对肿瘤前息肉微生物微环境的基本见解。

更新日期:2021-10-13
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