Meta-analysis of fecal metagenomes reveals global microbial signatures that are specific for colorectal cancer.

Meta-analysis of fecal metagenomes reveals global microbial signatures that are specific for colorectal cancer.
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粪便宏基因组的荟萃分析揭示了针对大肠癌的全球微生物特征。

DOI:
10.1038/s41591-019-0406-6
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发表时间:
2019-04
期刊:
影响因子:
82.9
通讯作者:
Zeller G
Zeller G
中科院分区:
医学1区
文献类型:
--
作者:
Wirbel J;Pyl PT;Kartal E;Zych K;Kashani A;Milanese A;Fleck JS;Voigt AY;Palleja A;Ponnudurai R;Sunagawa S;Coelho LP;Schrotz-King P;Vogtmann E;Habermann N;Niméus E;Thomas AM;Manghi P;Gandini S;Serrano D;Mizutani S;Shiroma H;Shiba S;Shibata T;Yachida S;Yamada T;Waldron L;Naccarati A;Segata N;Sinha R;Ulrich CM;Brenner H;Arumugam M;Bork P;Zeller G

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相关研究已经将微生物组的改变与许多人类疾病联系起来,但并不总是报告一致的结果,这需要进行交叉研究比较。在这里,对8项地理和技术上不同的结直肠癌(CRC,N = 768)粪便鸟枪宏基因组研究进行了荟萃分析,该研究控制了几个混杂因素,确定了一组29个物种的核心,这些物种在CRC宏基因组中显著富集(FDR <1 E-5)。来自单个研究的CRC签名在其他研究中保持准确性。通过多项研究的训练,我们提高了CRC的检测准确性和疾病特异性。CRC宏基因组的功能分析揭示了富集的蛋白质和粘蛋白催化剂基因和耗尽的碳水化合物降解基因。此外,我们推断CRC宏基因组中次级胆汁酸的产生增加,表明癌症相关肠道微生物与富含脂肪和肉类的饮食之间存在代谢联系。通过广泛的验证,这项荟萃分析牢固地建立了全球可推广的预测分类学和功能性微生物组CRC签名,作为未来诊断的基础。
Association studies have linked microbiome alterations with many human diseases, but not always reported consistent results, which necessitates cross-study comparisons. Here, a meta-analysis of eight geographically and technically diverse fecal shotgun metagenomic studies of colorectal cancer (CRC, N = 768), which was controlled for several confounders, identified a core set of 29 species significantly enriched in CRC metagenomes (FDR < 1E-5). CRC signatures derived from single studies maintained accuracy in other studies. By training on multiple studies we improved detection accuracy and disease specificity for CRC. Functional analysis of CRC metagenomes revealed enriched protein and mucin catabolism genes and depleted carbohydrate degradation genes. Moreover we inferred elevated production of secondary bile acids from CRC metagenomes suggesting a metabolic link between cancer-associated gut microbes and a fat- and meat-rich diet. Through extensive validations, this meta-analysis firmly establishes globally generalizable, predictive taxonomic and functional microbiome CRC signatures as a basis for future diagnostics.
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