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

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PubMed ID: 31171880

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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

Nat Med. Jun 2019. doi: 10.1038/s41591-019-0458-7

COMMENT: In this article the authors emphasize the multistep nature of the development of colorectal cancer. By means of the integration of shotgun metagenomics and metabolomics data taken from fecal samples the authors identify shifts in the metabolites and the microbes present at the gut. With regards to the microbiome composition they describe two kinds of communities, a group of organisms that increase their replication from early to later disease stages and another groups which showed replication increase only at early stages.

The combination of identified organisms and functional data from shotgun metagenomics with metabolomic results allowed the authors to build models that discriminate samples from early and late disease stages supporting and suggesting the use of these techniques for screening and early detection of the disease.


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.


Marina Manrique