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黏膜共生菌在结直肠癌早期阶段的基因组和功能特征分析。

Genomic and functional characterization of a mucosal symbiont involved in early-stage colorectal cancer.

机构信息

Department of Pathology, University of Washington, Seattle, WA 98195, USA; Center for Microbiome Science & Therapeutics, University of Washington, Seattle, WA 98195, USA.

Center for Microbiome Science & Therapeutics, University of Washington, Seattle, WA 98195, USA.

出版信息

Cell Host Microbe. 2021 Oct 13;29(10):1589-1598.e6. doi: 10.1016/j.chom.2021.08.013. Epub 2021 Sep 17.

DOI:10.1016/j.chom.2021.08.013
PMID:34536346
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8979638/
Abstract

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.

摘要

结直肠癌是全球范围内的一个主要健康关注点。越来越多的证据表明肠道微生物群在 CRC 的发生中起作用,这激发了人们对靶向这些微生物的方法的兴趣。然而,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发现了息肉患者和无息肉患者之间以及不同息肉亚型之间的明显微生物特征。我们发现从有息肉的患者中回收的脆弱拟杆菌与息肉附近粘膜中的炎症细胞因子水平之间存在相关性。进一步的分析表明,来自息肉患者的脆弱拟杆菌是 bft-阴性的,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。这项研究通过突出特定于菌株的基因组和蛋白质组差异以及微生物组中更广泛的组成差异,为癌前息肉的微生物微环境提供了基本的见解。

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