Integrated metabolome and transcriptome analyses provide insight into colon cancer development by the gut microbiota

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 significanceFecal metabolites, influenced by the gut microbiota, correlate with colon adenoma risk in a preclinical model of familial colon cancer.

Association between known risk factors and colorectal cancer risk among Indigenous people participating in the Ontario Familial Colon Cancer Registry

Introduction: Colorectal cancer is one of the most common cancers in Ontario and poses a high burden among many Indigenous populations. There are two aims for this short communication: (1) highlight colorectal risk factor findings from a population-based case-control study, (2) highlight trends and challenges of colorectal cancer research among Indigenous populations in Ontario.Methods: Prevalence of cigarette smoking, obesity, diet and family history of colorectal cancer were estimated using the Indigenous identifier in the Ontario Familial Colon Cancer Registry (OFCCR) from 1999-2007 and then compared using age-adjusted odds ratio (with 95% confidence intervals) between cases and controls.Results: There were 66 Indigenous cases and 23 Indigenous controls. Cigarette smoking and obesity were higher in cases, but not statistically significant.Discussion and Conclusions: Findings were consistent with previous literature among Indigenous populations. Colorectal cancer risk factor and screening uptake information is limited among Indigenous populations; however, self-reported screening data suggest low colorectal screening uptake. Small sample size and poor Indigenous identification questions make it challenging to comprehensively understand cancer risk factors and burden in these populations.