Microbiome and Colorectal Cancer

The trillions of microbes collectively referred to as the human microbiota inhabit the human body and establish a beneficial relationship with the host. It is clear however that dysbiosis impacting microbial diversity in the gut may lead to the development of inflammatory and malignant gastrointestinal diseases including colorectal cancer (CRC). We provide a literature review of the recent influx of information related to the alterations in gut microbiota composition that influences CRC incidence and progression.

A growing body of evidence implicates altered gut microbiota in the development of CRC. Profiles of CRC-associated microbiota have been shown to differ from those in healthy subjects and bacterial phylotypes vary depending on the primary tumor location. The compositional variation in the microbial profile is not restricted to cancerous tissue however and is different between cancers of the proximal and distal colons, respectively. More recently, studies have shed light on the “driver-passenger” model for CRC wherein, driver bacteria cause inflammation, increased cell proliferation and production of genotoxic substances to contribute towards mutational acquisition associated with adenoma-carcinoma sequence. These changes facilitate gradual replacement of driver bacteria by passengers that either promote or suppress tumor progression. Significant advances have also been made in associating individual bacterial species to consensus molecular subtypes (CMS) of CRC and this remarkable development is expected to galvanize scientific community into advancing therapeutic strategies for CRC.

Increasing evidence suggests a link between the intestinal microbiota and CRC development although the mechanisms through which the bacterial constituents of the microbiome contribute towards CRC are complex and yet to be fully fathomed. Thus, more exhaustive and mechanistic studies are needed to identify key interactions amongst diet, microbial community, and metabolites that help facilitate the adenoma-carcinoma sequence evolution in CRC. It is expected that development of therapeutics based on microbial association with CMS will likely facilitate the translation of molecular subtypes into the clinic for CRCs and potentially other malignancies.