Colorectal cancer mutational profiles correlate with defined microbial communities in the tumor microenvironment

Variation in the gut microbiome has been linked to colorectal cancer (CRC), as well as to host genetic variation. However, we do not know whether, in addition to baseline host genetics, somatic mutational profiles in CRC tumors interact with the surrounding tumor microbiome, and if so, whether these changes can be used to understand microbe-host interactions with potential functional biological relevance. Here, we characterized the association between CRC microbial communities and tumor mutations using microbiome profiling and whole-exome sequencing in 44 pairs of tumors and matched normal tissues. We found statistically significant associations between loss-of-function mutations in tumor genes and shifts in the abundances of specific sets of bacterial taxa, suggestive of potential functional interaction. This correlation allows us to statistically predict interactions between loss-of-function tumor mutations in cancer-related genes and pathways, including MAPK and Wnt signaling, solely based on the composition of the microbiome. In conclusion, our study shows that CRC microbiomes are correlated with tumor mutational profiles, pointing towards possible mechanisms of molecular interaction.Author summary: Although the gut microbiome—the collection of microorganisms that inhabit our gastrointestinal tract—has been implicated in colorectal cancer, colorectal tumors are caused by genetic mutations in host DNA. Here, we explored whether various mutations in colorectal tumors are correlated with specific changes in the bacterial communities that live in and on these tumors. We find that the genes and biological pathways that are mutated in tumors are correlated with variation in the composition of the microbiome. This study provides a step towards understanding interactions between tumor genes and the microbiome in colorectal cancer.