Colorectal Cancer-Associated Microbiome Patterns and Signatures.

Colorectal Cancer-Associated Microbiome Patterns and Signatures.
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DOI:
10.3389/fgene.2021.787176
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发表时间:
2021
影响因子:
3.7
通讯作者:
Nicolls MR
Nicolls MR
中科院分区:
生物学3区
文献类型:
--
作者:
Zhao L;Cho WC;Nicolls MR

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肠道微生物组是动态的,并受到饮食、年龄、地理位置和环境的影响。正常肠道微生物群的破坏(生态失调)与结直肠癌(CRC)的风险和进展密切相关。为了更好地识别和表征与 CRC 相关的生态失调,我们收集了六个具有匹配的正常对(如果有)的独立队列,以比较和探索微生物群及其与宿主的相互作用。比较癌组织和邻近非癌组织之间的微生物群落组成,我们发现肿瘤中耗尽的微生物多于富集的微生物。尽管队列之间存在分类差异,但与正常组织相比,结直肠癌中观察到正常微生物群(梭菌属和拟杆菌属成员)持续减少,口腔来源病原体(例如具核梭杆菌和微小单胞菌)显着富集。随后鉴定了中枢和中枢连接微生物组,以推断 CRC 中的微生物-微生物相互作用网络。此外,双聚类用于识别患者和微生物之间的连贯模式。在所调查的 6 个 CRC 队列中可以一致地识别出两种患者-微生物相互作用模式,称为 P0 和 P1。两种模式的微生物群落组成特征表明,P0 和 P1 患者的微生物 α 和 β 多样性存在显着差异,CRC 相关微生物群变化由广泛分布的分类单元的连续群体组成,而不是离散的肠型。与 P0 相比,P1 中的患者与邻近的正常组织相比,微生物 α 多样性降低,并且 P1 比 P0 和对照组拥有更多的口腔相关病原体。总的来说,我们的研究调查了与 CRC 相关的微生物组变化,并在多个独立队列中确定了可重复的微生物特征。更重要的是,我们发现CRC的异质性部分归因于微生物的多样性和组成差异及其与人类的相互作用。
The gut microbiome is dynamic and shaped by diet, age, geography, and environment. The disruption of normal gut microbiota (dysbiosis) is closely related to colorectal cancer (CRC) risk and progression. To better identify and characterize CRC-associated dysbiosis, we collected six independent cohorts with matched normal pairs (when available) for comparison and exploration of the microbiota and their interactions with the host. Comparing the microbial community compositions between cancerous and adjacent noncancerous tissues, we found that more microbes were depleted than enriched in tumors. Despite taxonomic variations among cohorts, consistent depletion of normal microbiota (members of Clostridia and Bacteroidia) and significant enrichment of oral-originated pathogens (such as Fusobacterium nucleatum and Parvimonas micra) were observed in CRC compared to normal tissues. Sets of hub and hub-connecting microbes were subsequently identified to infer microbe-microbe interaction networks in CRC. Furthermore, biclustering was used for identifying coherent patterns between patients and microbes. Two patient-microbe interaction patterns, named P0 and P1, can be consistently identified among the investigated six CRC cohorts. Characterization of the microbial community composition of the two patterns revealed that patients in P0 and P1 differed significantly in microbial alpha and beta diversity, and CRC‐associated microbiota changes consist of continuous populations of widespread taxa rather than discrete enterotypes. In contrast to the P0, the patients in P1 have reduced microbial alpha diversity compared to the adjacent normal tissues, and P1 possesses more oral-related pathogens than P0 and controls. Collectively, our study investigated the CRC-associated microbiome changes, and identified reproducible microbial signatures across multiple independent cohorts. More importantly, we revealed that the CRC heterogeneity can be partially attributed to the variety and compositional differences of microbes and their interactions to humans.
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