宏基因組和代謝組學揭示結直腸癌相關菌群的階段特異性
作者：
小柯機器人發布時間：2019/7/11 16:13:03
宏基因組和代謝組學揭示結直腸癌相關腸道菌群的階段特異性，這一成果由東京工業大學Takuji Yamada研究團隊獲得。2019年6月，國際知名學術期刊《Nature Medicine》發表了這一成果。
該課題組對616名接受結腸鏡檢查參與者的樣本進行了糞便宏基因組和代謝組學研究，以評估腸道微生物群和代謝物的分類學和功能特徵。在多發性息肉樣腺瘤和黏膜內癌的病例中以及更嚴重的病變中，微生物組和代謝組的變化明顯。研究人員發現了兩種不同的微生物群升高模式。首先， 具核梭桿菌的相對豐度（P<0.005）從黏膜內癌到更晚期持續升高。其次，僅在多發性息肉樣腺瘤和或黏膜內癌中，同時出現在黏膜內癌中的特應性小瘤和放線菌顯著增加（P<0.005）。代謝組學分析顯示，多發性息肉樣腺瘤和或多發性息肉樣腺瘤中支鏈胺基酸和苯丙氨酸顯著增加（P<0.005），膽汁酸（包括脫氧膽酸）顯著增加（P<0.005）。研究人員鑑定了宏基因組和代謝標記物，以區分黏膜內癌病例與健康對照組。課題組的大型隊列多組學數據表明，微生物組和代謝組的變化發生在結直腸癌發展的早期階段，這對可能病因的判定以及診斷具有重要意義。
據悉，在大多數的散發性結直腸癌中,腫瘤發生是一個多步驟的過程,包括基因組的改變與形態學變化。此外，越來越多的證據表明，人體腸道微生物組與結直腸癌的發展有關。
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