Colorectal cancer mutational profiles are correlated with defined microbial communities in the tumor microenvironment (!!!)

The human gut hosts at least 1,000 different microbial (bacterial, viral and a few fungal) species –– consisting of both commensal (living on or within another organism, and deriving benefit, but without apparently harming or benefiting that host.) and potentially pathogenic (disease-causing) members. In the context of colorectal cancer (CRC), bacteria in the microbiome very likely play a role in human cell signaling. For example, in CRC tumors that host the bacterium Fusobacterium nucleatum, the microbial genome encodes a virulence factor FadA that can activate the WNT/β-catenin pathway (an evolutionarily highly conserved WNT/ b-catenin pathway that regulates stem-cell pluripotency and cell-fate decisions during development).

Some researchers have attempted to predict CRC status, using the microbiome as a biomarker. By focusing on F. nucleatum, it might be possible to predict some clinically relevant features of the tumor present. There is a positive-trend association between the presence of F. nucleatum in CRCs in patients who eat a Western diet; because a minority of CRCs actually are host to F. nucleatum, however, the use of this species as a sole marker remains limited.

Authors [see preprint attached] characterized the association between CRC microbial communities and tumor mutations, using microbiome profiling and whole-exome sequencing (WES) in 44 pairs of tumors and matched normal tissues. They found statistically significant associations between loss-of-function mutations in tumor genes and shifts in abundance of specific sets of bacterial taxa –– suggesting potentially important functional interaction. Authors suggest that this correlation might allow us, in the near future, to predict statistically the interactions between loss-of-function tumor mutations in cancer-related genes and specific pathways. These include MAPK/ERK-signaling (mitogen-activated protein kinases, a highly conserved family of protein kinases involved in many fundamental cellular processes –– e.g. proliferation, differentiation, motility, stress response, apoptosis, & survival.) and WNT-signaling, solely based on the composition of the microbiome. This knowledge might help clinicians in choosing the best chemotherapeutic agents, as well as in predicting prognosis of the individual patient.

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