Fecal Microbiome and Metabolome Differences Between Colorectal Cancer Patients and Healthy Adults

Objective: The study objective was to identify intestinal bacteria that are either over or under-represented in colorectal cancer (CRC) using fecal profiling and to correlate associated fecal metabolites to provide a snapshot of how microbial functions influences CRC development. Methods/Study Design: Fecal samples were collected from healthy adults (n=10) and colorectal cancer patients (n=11) prior to surgery at the University of Colorado Health-Poudre Valley Hospital in Fort Collins, CO. The V4 region of the 16s rRNA gene was pyrosequenced on a 454 platform and analyzed using Mothur Version 1.18. Metabolites were extracted using acidified water for short chain fatty acids (SCFA) and 3:2:2 isopropanol:acetonitrile:water to obtain global metabolite profiles utilizing Gas Chromatography-Mass Spectrometry (GC-MS). Results: There were no significant differences in the overall microbial community structure associated with disease state, but several bacterial genera, particularly butyrate-producing species, were under-represented in the CRC samples, while a mucin-degrading species, Akkermansia muciniphila, was about 4-fold higher in CRC (p<0.01). GC-MS profiling revealed that there were higher levels of amino acids in stool samples from CRC patients and higher poly and monounsaturated fatty acids and a conjugated bile acid in stool from healthy adults (p<0.01). Conclusions: Using integrated “omics” approaches may prove a useful tool in identifying functional groups of gastrointestinal bacteria and their associated metabolites as novel therapeutic and chemopreventive targets.