期刊
NATURE MEDICINE
卷 25, 期 6, 页码 968-+出版社
NATURE PORTFOLIO
DOI: 10.1038/s41591-019-0458-7
关键词
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资金
- National Cancer Center Research and Development Fund [25-A-4, 28-A-4, 29-A-6]
- Practical Research Project for Rare/Intractable Diseases from the Japan Agency for Medical Research and Development (AMED) [JP18ek0109187, JP18jk0210009]
- AMED-CREST [JP18gm0710003]
- JST (Japan Science and Technology Agency)-PRESTO [JPMJPR1537, JPMJPR1507]
- JSPS (Japan Society for the Promotion of Science) KAKENHI [16H04901, 17H05654, 18H04805, 16J10135, 142558, 221S0002]
- Joint Research Project of the Institute of Medical Science, the University of Tokyo [2017-2107]
- Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives, Osaka University
- Takeda Science Foundation
- Suzuken Memorial Foundation [H25-2-11]
- Grants-in-Aid for Scientific Research [16J10135] Funding Source: KAKEN
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.
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