Microbiota and the metabolites they produce within the large intestine interact with the host epithelia under the influence of a range of host-derived metabolic, immune, and homeostatic factors. This complex host-microbe interaction affects intestinal tumorigenesis but established microbial or metabolite profiles predicting colorectal cancer (CRC) risk are missing. Here we describe alterations in fecal bacteria and volatile organic compounds (VOC) in healthy (Non-Adenoma, NA) versus CRC prone (High-Risk Adenoma, HRA) individuals. Analyzing samples from 117 participants undergoing routine colonoscopy we highlight the higher abundance of Proteobacteria and Parabacteroides distasonis, and the lower abundance of Lachnospiraceae species, Roseburia faecis, Blautia luti, Fusicatenibacter saccharovorans, Eubacterium rectale and Phascolarctobacterium faecium, in the fecal samples of HRA individuals. Volatolomic analysis reveals higher concentration in the feces of HRA individuals of 5 compounds, isobutyric acid, methyl butyrate, methyl propionate, 2-hexanone and 2-pentanone. Interestingly, there is a level of complexity revealed by assessing fecal bacteria-VOC associations and another one by assessing differences in these associations between NA and HRA individuals. For example, isobutyric acid corelates positively with the Lachnospiraceae incertae sedis and Bacteroides genera in NA individuals, and negatively in HRA individuals. In contrast, Coprococcus and Colinsella genera correlate negatively with isobutyric acid in NA individuals, and positively in HRA individuals. The described differences in the fecal microbiota and VOC profiles and their associations in NA versus HRA individuals indicate the significance of multiple levels of combinatorial analysis towards the identification of testable CRC risk biomarkers.
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