The Role of the Microbiome on the Pathogenesis and Treatment of Colorectal Cancer

Abstract

The gut microbiome has long been known to play a role in various aspects of health modulation, including the pathogenesis of colorectal cancer (CRC). With immunotherapy recently emerging as a successful treatment in microsatellite instability high (MSI-high) CRC, and with a newly demonstrated involvement of the gut microbiome in the modulation of therapeutic responses, there has been an explosion of research into the mechanisms of microbial effects on CRC. Harnessing and reprogramming the microbiome may allow for the expansion of these successes to broader categories of CRC, the prevention of CRC in high-risk patients, and the enhancement of standard treatments. In this review, we pull together both well-documented phenomena and recent discoveries that pertain to the microbiome and CRC. We explore the microbial mechanisms associated with CRC pathogenesis and progression, recent advancements in CRC systemic therapy, potential options for diagnosis and prevention, as well as directions for future research.

Keywords: cancer; carcinogenesis; chemotherapy; colorectal cancer; diagnosis; dysbiosis; immunotherapy; microbes; microbiome; prevention; tumor microenvironment.

Figure 1

Effects of the microbiome on the pathogenesis and progression of colorectal cancer. Multiple different aspects of the microbiome have been proposed to play a role in the pathogenesis and progression of colorectal cancer, including dysbiosis of the bacterial and viral microbiomes, the biofilms and toxins associated with bacterial dysbiosis, and microbe-mitochondrial crosstalk altering mitochondrial function.

Figure 2

Preventative, diagnostic, and therapeutic options that influence and are under the influence of the microbiome. Interventions such as chemotherapy and aspirin prophylaxis have been shown to influence or be influenced by certain aspects of the microbiome. Research continues to provide or suggest newer management strategies as well, such as use of immunotherapy in colorectal cancer, development of personalized biomarkers, and consideration of fecal microbiota transplant (FMT), all of which also have complex interactions with the gut microbiome.