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

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 SogaKen Kurokawa, Atsushi Toyoda, Yoshitoshi Ogura, Tetsuya Hayashi, Masanori Hatakeyama, Hitoshi Nakagama, Yutaka Saito, Shinji Fukuda, Tatsuhiro Shibata, Takuji Yamada

Research output: Contribution to journalLetter

3 Citations (Scopus)

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 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.

Original languageEnglish
Pages (from-to)968-976
Number of pages9
JournalNature medicine
Volume25
Issue number6
DOIs
Publication statusPublished - Jun 1 2019

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Metagenomics
Metabolomics
Colorectal Neoplasms
Carcinoma
Phenotype
Microbiota
Branched Chain Amino Acids
Deoxycholic Acid
Metabolites
Metabolome
Bile Acids and Salts
Phenylalanine
Adenoma
Fusobacterium nucleatum
Actinomyces
Colonoscopy
Gastrointestinal Microbiome
Carcinogenesis

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Yachida, S., Mizutani, S., Shiroma, H., Shiba, S., Nakajima, T., Sakamoto, T., ... Yamada, T. (2019). Metagenomic and metabolomic analyses reveal distinct stage-specific phenotypes of the gut microbiota in colorectal cancer. Nature medicine, 25(6), 968-976. https://doi.org/10.1038/s41591-019-0458-7

Metagenomic and metabolomic analyses reveal distinct stage-specific phenotypes of the gut microbiota in colorectal cancer. / Yachida, Shinichi; Mizutani, Sayaka; Shiroma, Hirotsugu; Shiba, Satoshi; Nakajima, Takeshi; Sakamoto, Taku; Watanabe, Hikaru; Masuda, Keigo; Nishimoto, Yuichiro; Kubo, Masaru; Hosoda, Fumie; Rokutan, Hirofumi; Matsumoto, Minori; Takamaru, Hiroyuki; Yamada, Masayoshi; Matsuda, Takahisa; Iwasaki, Motoki; Yamaji, Taiki; Yachida, Tatsuo; Soga, Tomoyoshi; Kurokawa, Ken; Toyoda, Atsushi; Ogura, Yoshitoshi; Hayashi, Tetsuya; Hatakeyama, Masanori; Nakagama, Hitoshi; Saito, Yutaka; Fukuda, Shinji; Shibata, Tatsuhiro; Yamada, Takuji.

In: Nature medicine, Vol. 25, No. 6, 01.06.2019, p. 968-976.

Research output: Contribution to journalLetter

Yachida, S, Mizutani, S, Shiroma, H, Shiba, S, Nakajima, T, Sakamoto, T, Watanabe, H, Masuda, K, Nishimoto, Y, Kubo, M, Hosoda, F, Rokutan, H, Matsumoto, M, Takamaru, H, Yamada, M, Matsuda, T, Iwasaki, M, Yamaji, T, Yachida, T, Soga, T, Kurokawa, K, Toyoda, A, Ogura, Y, Hayashi, T, Hatakeyama, M, Nakagama, H, Saito, Y, Fukuda, S, Shibata, T & Yamada, T 2019, 'Metagenomic and metabolomic analyses reveal distinct stage-specific phenotypes of the gut microbiota in colorectal cancer', Nature medicine, vol. 25, no. 6, pp. 968-976. https://doi.org/10.1038/s41591-019-0458-7
Yachida, Shinichi ; Mizutani, Sayaka ; Shiroma, Hirotsugu ; Shiba, Satoshi ; Nakajima, Takeshi ; Sakamoto, Taku ; Watanabe, Hikaru ; Masuda, Keigo ; Nishimoto, Yuichiro ; Kubo, Masaru ; Hosoda, Fumie ; Rokutan, Hirofumi ; Matsumoto, Minori ; Takamaru, Hiroyuki ; Yamada, Masayoshi ; Matsuda, Takahisa ; Iwasaki, Motoki ; Yamaji, Taiki ; Yachida, Tatsuo ; Soga, Tomoyoshi ; Kurokawa, Ken ; Toyoda, Atsushi ; Ogura, Yoshitoshi ; Hayashi, Tetsuya ; Hatakeyama, Masanori ; Nakagama, Hitoshi ; Saito, Yutaka ; Fukuda, Shinji ; Shibata, Tatsuhiro ; Yamada, Takuji. / Metagenomic and metabolomic analyses reveal distinct stage-specific phenotypes of the gut microbiota in colorectal cancer. In: Nature medicine. 2019 ; Vol. 25, No. 6. pp. 968-976.
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AU - Yachida, Shinichi

AU - Mizutani, Sayaka

AU - Shiroma, Hirotsugu

AU - Shiba, Satoshi

AU - Nakajima, Takeshi

AU - Sakamoto, Taku

AU - Watanabe, Hikaru

AU - Masuda, Keigo

AU - Nishimoto, Yuichiro

AU - Kubo, Masaru

AU - Hosoda, Fumie

AU - Rokutan, Hirofumi

AU - Matsumoto, Minori

AU - Takamaru, Hiroyuki

AU - Yamada, Masayoshi

AU - Matsuda, Takahisa

AU - Iwasaki, Motoki

AU - Yamaji, Taiki

AU - Yachida, Tatsuo

AU - Soga, Tomoyoshi

AU - Kurokawa, Ken

AU - Toyoda, Atsushi

AU - Ogura, Yoshitoshi

AU - Hayashi, Tetsuya

AU - Hatakeyama, Masanori

AU - Nakagama, Hitoshi

AU - Saito, Yutaka

AU - Fukuda, Shinji

AU - Shibata, Tatsuhiro

AU - Yamada, Takuji

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