The microbiome and metabolome in colorectal cancer (CRC)

Yachida S, Mizutani S, Shiroma H, et al. Metagenomic and metabolomic analyses reveal distinct stage-specific phenotypes of the gut microbiota in colorectal cancer. Nat Med 2019; 25(6):968–76.

The role of the microbiome is of growing interest in cancer. This large cohort multiomics study examined microbiome changes in the early stages of CRC. Faecal shotgun metagenomic and metabolomic data were collected from 616 and 406 patients, respectively. Patients were classified into groups according to colonoscopy findings: healthy (normal colonoscopy or up to two small polyps <5 mm), more than three polyps with low-grade dysplasia, any intramucosal cancer (or polyp with high-grade dysplasia) and colorectal cancer. Only adenomatous polyps were included; serrated polyps were excluded. The number of reads increased by stage of CRC, hence encompassing a higher proportion of the genome. Two distinct patterns of microbiome changes were described. First, Fusobacterium nucleatum was elevated in intramucosal cancer and increased gradually by stage of cancer. F. nucleatum is known to be associated with CRC. Second, Atopobium parvulum and Actinomyces odontolyticus, which co-occurred in intramucosal cancer, were elevated only in multiple adenomas and intramucosal cancer. A. parvulum is a species of hydrogen sulphide-producing bacteria, which are associated with IBD and cancer. Metabolomic data showed that branched-chain amino acids and phenylalanine were increased in intramucosal cancer. Bile acids including deoxycholate were increased both in patients with multiple polyps and intramucosal cancer. In summary, metagenomic and metabolomic shifts occurred early in the cancer pathway. The aetiological significance of these changes is unclear, but diagnostically they could be used as markers to discriminate healthy controls, early and late disease stages. Cancer progression may be influenced not only by genetics but also by the microbiota and their related metabolism.

A single cell atlas of human liver

Aizarani N, Saviano A, Sagar, et al. A human liver cell atlas reveals heterogeneity and epithelial …