Integrative analysis of the mouse fecal microbiome and metabolome reveal dynamic phenotypes in the development of colorectal cancer.

Abstract

The gut microbiome and its interaction with host have been implicated as the causes and regulators of colorectal cancer (CRC) pathogenesis. However, few studies comprehensively investigate the compositions of gut bacteria and their interactions with host at the early inflammatory and cancerous stages of CRC. In this study, mouse fecal samples collected at inflammation and CRC were subjected to microbiome and metabolome analyses. The datasets were analyzed individually and integratedly using various bioinformatics approaches. Great variations in gut microbiota abundance and composition were observed in inflammation and CRC. The abundances of Bacteroides, S24-7_group_unidifineted, and Allobaculum were significantly changed in inflammation and CRC. The abundances of Bacteroides and Allobaculum were significantly different between inflammation and CRC. Furthermore, strong excluding and appealing microbial interactions were found in the gut microbiota. CRC and inflammation presented specific fecal metabolome profiling. Fecal metabolomic analysis led to the identification and quantification of 1,138 metabolites with 32 metabolites significantly changed in CRC and inflammation. 1,17-Heptadecanediol and 24,25,26,27-Tetranor-23-oxo-hydroxyvitamin D3 were potential biomarkers for CRC. 3α,7β,12α-Trihydroxy-6-oxo-5α-cholan-24-oic Acid and NNAL-N-glucuronide were potential biomarkers for inflammation. The significantly changed bacterial species and metabolites contribute to inflammation and CRC diagnosis. Integrated microbiome and metabolomic analysis correlated microbes with host metabolites, and the variated microbe-metabolite association in inflammation and CRC suggest that microbes facilitate tumorigenesis of CRC through interfering host metabolism.