A group of Japanese scientists reported on 6 June 2019 in the Nature Medicine findings from a large-cohort multi-omics study which indicate that shifts in the microbiome and metabolome occur from the very early stages of the development of colorectal cancer. The findings are of possible aetiological and diagnostic importance.
The authors wrote in study background that in most cases of sporadic colorectal cancers, tumourigenesis is a multistep process that involves 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.
The study team performed foecal 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.
The investigators 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.
The study team identified metagenomic and metabolomic markers to discriminate cases of intramucosal carcinoma from the healthy controls. They concluded that shifts in the microbiome and metabolome occur early in development of colorectal cancer.
This work was supported by grants from the National Cancer Center Research and Development Fund, Practical Research Project for Rare/Intractable Diseases from the Japan Agency for Medical Research and Development (AMED), AMED-CREST, Japan Science and Technology Agency-PRESTO, Japan Society for the Promotion of Science KAKENHI, Joint Research Project of the Institute of Medical Science, the University of Tokyo, Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives, Osaka University, the Takeda Science Foundation and Suzuken Memorial Foundation.
Yachida S, Mizutani S, Shiroma H, et al. Metagenomic and metabolomic analyses reveal distinct stage-specific phenotypes of the gut microbiota in colorectal cancer. Nature Medicine; Published online 6 June2019. doi: 10.1038/s41591-019-0458-7.