RT Journal Article
SR Electronic
T1 Integrated metabolome and transcriptome analyses provide insight into colon cancer development by the gut microbiota
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.07.24.220269
DO 10.1101/2020.07.24.220269
A1 Susheel Bhanu Busi
A1 Zhentian Lei
A1 Lloyd W. Sumner
A1 James Amos-Landgraf
YR 2020
UL http://biorxiv.org/content/early/2020/07/25/2020.07.24.220269.abstract
AB Colon cancer onset and progression is strongly associated with the presence, absence, or differences in relative abundances of certain microbial taxa in the gastrointestinal tract. However, specific mechanisms affecting disease susceptibility related to complex commensal bacterial mixtures are poorly understood. We used a multi-omics approach to determine how differences in the complex gut microbiome (GM) influence the metabolome and host transcriptome and ultimately affect susceptibility to adenoma development in a preclinical rat model of colon cancer. Fecal samples from rats harboring distinct complex GMs were analyzed using ultra-high performance liquid chromatography mass spectrometry (UHPLC-MS). We collected samples prior to observable disease onset and identified putative metabolite profiles that predicted future disease severity, independent of GM status. Transcriptome analyses performed after disease onset from normal epithelium and tumor tissues between the high and low tumor GMs suggests that the GM is correlated with altered host gene expression. Integrated pathway (IP) analyses of the metabolome and transcriptome based on putatively identified metabolic features indicate that bile acid biosynthesis was enriched in rats with high tumors (GM:F344) along with increased fatty acid metabolism and mucin biosynthesis. These data emphasize the utility of using untargeted metabolomics to reveal signatures of susceptibility and resistance and integrated analyses to reveal common pathways that are likely to be universal targets for intervention.Statement of significance Fecal metabolites, influenced by the gut microbiota, correlate with colon adenoma risk in a preclinical model of familial colon cancer.Competing Interest StatementThe authors have declared no competing interest.