Tumour-associated and non-tumour-associated microbiota in colorectal cancer.

Tumour-associated and non-tumour-associated microbiota in colorectal cancer.
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DOI:
10.1136/gutjnl-2015-309595
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发表时间:
2017-04
期刊:
Gut
影响因子:
24.5
通讯作者:
O'Toole PW
O'Toole PW
中科院分区:
医学1区
文献类型:
--
作者:
Flemer B;Lynch DB;Brown JM;Jeffery IB;Ryan FJ;Claesson MJ;O'Riordain M;Shanahan F;O'Toole PW

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尚未确定在多项研究中统一结直肠癌(CRC)微生物群的特征。除方法学差异外,异质性可能由微生物和宿主反应差异引起,这在本研究中得到了解决。我们前瞻性地研究了结肠微生物群和特异性宿主反应基因的表达,使用粪便和粘膜样本(“ON”和“OFF”肿瘤,近端和远端),来自59名接受CRC手术的患者,21名息肉患者和56名健康对照。通过16 S rRNA扩增子测序确定微生物群组成;通过实时定量PCR定量参与CRC进展和免疫应答的宿主基因的表达。CRC患者的微生物群与对照组不同,但变化并不限于癌组织。检测到远端和近端癌症之间的差异,并且粪便微生物群仅部分反映CRC中的粘膜微生物群。CRC患者可以根据粘膜相关细菌共丰度组(CAG)的更高水平结构进行分层,这些结构类似于先前制定的肠型概念。其中,拟杆菌属簇1和厚壁菌属簇1在CRC粘膜中的丰度降低,而拟杆菌属簇2、厚壁菌属簇2、病原体簇和普雷沃氏菌属簇在CRC粘膜中的丰度增加。CRC相关的CAG与宿主免疫炎症反应基因的表达差异相关。CRC相关的微生物群特征与健康受试者不同,并与不同的粘膜基因表达谱有关。微生物群的组成变化并不局限于癌组织,并且在远端和近端癌症之间存在差异。
A signature that unifies the colorectal cancer (CRC) microbiota across multiple studies has not been identified. In addition to methodological variance, heterogeneity may be caused by both microbial and host response differences, which was addressed in this study. We prospectively studied the colonic microbiota and the expression of specific host response genes using faecal and mucosal samples (‘ON’ and ‘OFF’ the tumour, proximal and distal) from 59 patients undergoing surgery for CRC, 21 individuals with polyps and 56 healthy controls. Microbiota composition was determined by 16S rRNA amplicon sequencing; expression of host genes involved in CRC progression and immune response was quantified by real-time quantitative PCR. The microbiota of patients with CRC differed from that of controls, but alterations were not restricted to the cancerous tissue. Differences between distal and proximal cancers were detected and faecal microbiota only partially reflected mucosal microbiota in CRC. Patients with CRC can be stratified based on higher level structures of mucosal-associated bacterial co-abundance groups (CAGs) that resemble the previously formulated concept of enterotypes. Of these, Bacteroidetes Cluster 1 and Firmicutes Cluster 1 were in decreased abundance in CRC mucosa, whereas Bacteroidetes Cluster 2, Firmicutes Cluster 2, Pathogen Cluster and Prevotella Cluster showed increased abundance in CRC mucosa. CRC-associated CAGs were differentially correlated with the expression of host immunoinflammatory response genes. CRC-associated microbiota profiles differ from those in healthy subjects and are linked with distinct mucosal gene-expression profiles. Compositional alterations in the microbiota are not restricted to cancerous tissue and differ between distal and proximal cancers.
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发表时间: 2013-01-07
影响因子: 14.9
作者:
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发表时间: 2012-07-06
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发表时间: 2011-05-12
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DOI: 10.1158/0008-5472.can-10-2907
发表时间: 2011-02-15
期刊: CANCER RESEARCH
影响因子: 11.2
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期刊: GENOME RESEARCH
影响因子: 7
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