宏基因组和代谢组学揭示结直肠癌相关肠道菌群的阶段特异性，这一成果由东京工业大学Takuji Yamada研究团队获得。2019年6月，国际知名学术期刊《Nature Medicine》发表了这一成果。

该课题组对616名接受结肠镜检查参与者的样本进行了粪便宏基因组和代谢组学研究，以评估肠道微生物群和代谢物的分类学和功能特征。在多发性息肉样腺瘤和粘膜内癌的病例中以及更严重的病变中，微生物组和代谢组的变化明显。研究人员发现了两种不同的微生物群升高模式。首先， 具核梭杆菌的相对丰度（P<0.005）从粘膜内癌到更晚期持续升高。其次，仅在多发性息肉样腺瘤和或粘膜内癌中，同时出现在粘膜内癌中的特应性小瘤和放线菌显著增加（P<0.005）。代谢组学分析显示，多发性息肉样腺瘤和或多发性息肉样腺瘤中支链氨基酸和苯丙氨酸显著增加（P<0.005），胆汁酸（包括脱氧胆酸）显著增加（P<0.005）。研究人员鉴定了宏基因组和代谢标记物，以区分粘膜内癌病例与健康对照组。课题组的大型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早期阶段，这对可能病因的判定以及诊断具有重要意义。

据悉，在大多数的散发性结直肠癌中,肿瘤发生是一个多步骤的过程,包括基因组的改变与形态学变化。此外，越来越多的证据表明，人体肠道微生物组与结直肠癌的发展有关。

附：英文原文

Title: Metagenomic and metabolomic analyses reveal distinct stage-specific phenotypes of the gut microbiota in colorectal cancer

Author: Shinichi Yachida, Sayaka Mizutani, Hirotsugu Shiroma, Satoshi Shiba, Takeshi Nakajima, Taku Sakamoto, Hikaru Watanabe, Keigo Masuda, Yuichiro Nishimoto, Masaru Kubo, Fumie Hosoda, Hirofumi Rokutan, Minori Matsumoto, Hiroyuki Takamaru, Masayoshi Yamada, Takahisa Matsuda, Motoki Iwasaki, Taiki Yamaji, Tatsuo Yachida, Tomoyoshi Soga, Ken Kurokawa, Atsushi Toyoda, Yoshitoshi Ogura, Tetsuya Hayashi, Masanori Hatakeyama, Hitoshi Nakagama, Yutaka Saito, Shinji Fukuda, Tatsuhiro Shibata, Takuji Yamada

Issue&Volume: Volume 25 Issue 6，June 2019

Abstract: 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 616participants 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.

DOI: 10.1038/s41591-019-0458-7

Source:https://www.nature.com/articles/s41591-019-0458-7