结直肠癌黏膜组织来源的大肠杆菌菌株间遗传和功能差异研究
常宇骁 , 李享 , 丁磊 , 杨超 , 潘志远 , 韩妮 , 崔玉军 , 智发朝 , 杨瑞馥 , 高宏 , 毕玉晶
工程(英文) ›› 2022, Vol. 16 ›› Issue (9) : 210 -219.
结直肠癌黏膜组织来源的大肠杆菌菌株间遗传和功能差异研究
Genetic and Functional Differences of Escherichia coli Strains from Colorectal Cancer Mucosal Tissues
结直肠癌是全球第三大癌症。宏基因组学已被广泛用于基于细菌属或种水平的比较来分析肠道微生物群与结直肠癌之间的关系,为结直肠癌发展中的生态失调提供了证据。然而,这种分析并不能为我们提供菌株水平的信息,进而理解一种细菌在结直肠癌发生发展中菌株水平的作用。本文利用培养组学方法分离结直肠癌黏膜样本,并选择了158株大肠杆菌,通过系统发育分析和炎症诱导实验,揭示它们在基因组学和功能上的差异。基因组比较可以将这些菌株分为5个系统群。选择代表性菌株进行THP-1细胞(人白血病单核细胞)Transwell实验以及动物实验,结果显示不同菌株经刺激后,细胞因子水平有显著性差异。进一步的生物信息学分析揭示了不同系统群间单核苷酸多态性、基因和代谢途径的不同特征,这些结果有助于了解这些菌株之间的表型差异。细菌菌株在基因组学和功能上的差异表明,菌株水平上的功能差异可以进一步了解宿主与肠道细菌的相互作用机制。
Colorectal cancer (CRC) is the third leading cancer globally. Metagenomics has been widely used to analyze the association between the gut microbiota and CRC based on bacterial genus- or species-level comparisons, providing evidence of dysbiosis in CRC development. However, this kind of analysis is unable to provide strain-level information for understanding the individual role of a species in CRC. Here, we used culturomics to isolate CRC mucosal samples and selected 158 Escherichia coli strains to reveal their differences in both genomics and functions by means of phylogenetic analysis and inflammatory induction based on cell and animal experiments. Through genomic comparison, these strains were divided into five phylogroups. The representative strains of each phylogroup significantly induced different levels of cytokine secretion by human leukemic monocyte (THP-1 cell)-based Transwell and animal experiments. Further bioinformatic analysis revealed different profiles of single-nucleotide polymorphisms, genes, and metabolic pathways in the different phylogroups, which can improve the current understanding of the phenotypic differences between these strains. The strain differences revealed in both genomics and functions indicate that the microbiota's function at the strain level should be investigated in order to understand the interacting mechanisms between hosts and gut bacteria.
结直肠癌 / 肠道菌群 / 培养组学 / 大肠杆菌 / 菌株水平
Colorectal cancer / Gut microbiota / Culturomics / Escherichia coli / Strain level
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