Metagenomic and metabolomic analyses reveal distinct stage-specific phenotypes of the gut microbiota in colorectal cancer
Metagenomic and metabolomic analyses reveal distinct stage-specific phenotypes of the gut microbiota in colorectal cancer
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DOI：
10.1038/s41591-019-0458-7
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发表时间：
2019-06-01
期刊：
影响因子：
82.9
通讯作者：
Yamada, Takuji
中科院分区：
文献类型：
--
作者：
Yachida, Shinichi;Mizutani, Sayaka;Yamada, Takuji
在大多数散发性结直肠癌病例中，肿瘤发生是一个多步骤的过程，包括与形态学改变平行的基因组改变。此外，越来越多的证据表明，人类肠道微生物组与结直肠癌的发展有关。在这里，我们对来自616名接受结肠镜检查的参与者的大型队列的样本进行了粪便宏基因组学和代谢组学研究，以评估肠道微生物群和代谢物的分类和功能特征。在多发性息肉样腺瘤和粘膜内癌的病例中，除了更晚期的病变外，微生物组和代谢组的变化也很明显。我们发现了两种不同的微生物组升高模式。第一，具核梭杆菌的相对丰度。从粘膜内癌到更晚期，持续显著升高（P < 0.005）。其次，粘膜内癌中共存的小奇异菌和溶牙放线菌仅在多发性息肉样腺瘤和/或粘膜内癌中显著增加（P < 0.005）。代谢物组学分析显示，支链氨基酸和苯丙氨酸在粘膜内癌中显著升高（P < 0.005），胆汁酸（包括脱氧胆酸盐）在多发性息肉样腺瘤和/或粘膜内癌中显著升高（P < 0.005）。我们鉴定了宏基因组学和代谢组学标记物，以区分粘膜内癌病例和健康对照。我们的大队列多组学数据表明，微生物组和代谢组的变化发生在结直肠癌发展的非常早期阶段，这可能具有病因学和诊断的重要性。
In most cases of sporadic colorectal cancers, tumorigenesis is a multistep process, involving genomic alterations in parallel with morphologic changes. In addition, accumulating evidence suggests that the human gut microbiome is linked to the development of colorectal cancer. Here we performed fecal metagenomic and metabolomic studies on samples from a large cohort of 616 participants who underwent colonoscopy to assess taxonomic and functional characteristics of gut microbiota and metabolites. Microbiome and metabolome shifts were apparent in cases of multiple polypoid adenomas and intramucosal carcinomas, in addition to more advanced lesions. We found two distinct patterns of microbiome elevations. First, the relative abundance of Fusobacterium nucleatum spp. was significantly (P < 0.005) elevated continuously from intramucosal carcinoma to more advanced stages. Second, Atopobium parvulum and Actinomyces odontolyticus, which co-occurred in intramucosal carcinomas, were significantly (P < 0.005) increased only in multiple polypoid adenomas and/or intramucosal carcinomas. Metabolome analyses showed that branched-chain amino acids and phenylalanine were significantly (P < 0.005) increased in intramucosal carcinomas and bile acids, including deoxycholate, were significantly (P < 0.005) elevated in multiple polypoid adenomas and/or intramucosal carcinomas. We identified metagenomic and metabolomic markers to discriminate cases of intramucosal carcinoma from the healthy controls. Our large-cohort multi-omics data indicate that shifts in the microbiome and metabolome occur from the very early stages of the development of colorectal cancer, which is of possible etiological and diagnostic importance.