In the literature: August 2018

Correspondence to Professor Andrés Cervantes; andres. cervantes@ uv. es © Author (s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ on behalf of the European Society for Medical Oncology. MetagenoMiC and MetaboloMiC analyses reveal distinCt stage-speCifiC phenotypes of the gut MiCrobiota in ColoreCtal CanCer Several analyses have been conducted to identify factors, which might promote colorectal cancer (CRC) development. As the immune system appeared as a fundamental actor in the scene, a growing interest was focusing on the microbioma. Alterations in the gut ecosystem have been implicated in the changes in human health and disease. Intestinal metabolites have also been recognised and associated with CRC. In a relevant article recently published in Nature Medicine by several academic institutions from Japan, a wide metagenomic and metabolomic analysis collecting data from more than 500 subjects to better characterise the relation between intestinal flora and the development of CRC was performed. Patients were divided into nine different subgroups according to colonoscopy and histological findings, as well as for risk factors such as smoking, alcohol assumption and body mass index. Human genome content was analysed and it was significantly higher in various stages of CRC than controls with Bacteroides and Prevotella being the major contributors to human gut enterotypes. Principal component analysis (PCA) identified the two most variable clusters in all subjects and in 251 healthy controls. The PCA showed large variation in dihydrouracil and urea in addition to propionate and butyrate in the population. Despite this, none of the stages, tumour locations or genders was associated with variation in metabolite profiles. Nevertheless, compared with the healthy controls, microbiome was highly distinct across stages. A number of species in the phyla Firmicutes, Fusobacteria and Bacteroidetes was increasing with the degree of malignancy and a large number of species were elevated only when multiple polyps were found. Two patterns of significant species elevation were highlighted. The first increased across early to later stages, whereas the second was elevated only in the early stages. In addition, new species associated with CRC were identified. In total, 65 metabolites showed significant differences in at least one of the stages compared with healthy controls. This publication shows that microbiome and metabolome shift in multiple polyposis and T0/Tis in addition to the more advanced stages. Two patterns of species elevation were found: the first consisted of a continuous increase from early stages onwards, whereas the other showed elevation only in early stages. Nevertheless, it was no longer possible to clarify any potential microbial involvement in stages prior to the formation of adenomas and more detailed causalities between microbiome and/or metabolome and tumours, so that a longitudinal investigation is needed. In addition, clarification of relationships between the gut microbiome and tumour molecular characteristics in individual patients with CRC will be necessary to understand the roles of the microbiome in CRC carcinogenesis. Metagenomic and metabolomic data derived from faecal and/or tissue samples from patients with hereditary or suspected hereditary diseases and patients with serrated lesions may also be analysed to clarify other aspects of CRC tumorigenesis. In conclusion, the present study highlights that dynamic shifts occur in microbial composition and metabolites changes during multistep CRC progression, suggesting their potential role in cancer progression, although it is not clear whether these species and metabolites directly cause tumorigenesis. Further investigations are needed to better define the role of microorganisms in CRC.