Colorectal cancer (CRC) is the second leading cause of cancer-related death worldwide, and its incidence is increasing—particularly in people under 50 years of age.
Unlike some other cancers the cause is as yet unknown, but there is a growing body of literature that points to environmental factors such as diet being a key contributor for up to 90% of the cases. Altered microbiota, that are reputedly responsible for the growth of tumours, have been identified in patients with CRC, so a research team from NDORMS set out to review whether these microbes contribute to the disease or represent a bystander effect.
In a new paper published in Nature, lead author Alina Janney reviewed published studies looking at interactions between a host and microbiota in CRC and considered how host maladaptation promoted tumour growth.
"We wanted to provide our readers an overview of this exciting new field in science which has great potential to lead to improved colon cancer treatments," said Alina Janney, DPhil student at NDORMS.
The review found:
- Dysbiosis in CRC: Pro-carcinogenic microbes are found in greater numbers in individuals with CRC than in healthy people. This different taxonomy is known as dysbiosis. Some of the microbial species found in CRC have been linked to causing cancer.
- Genotoxicity induced by CRC-associated bacteria: A number of pathogens associated with CRC cause DNA damage which can bring about carcinogenic effects. E. Coli has been shown to have a direct effect on cell mutations in the intestine.
- The effect of microorganism-driven metabolism: As well as having the potential to be directly carcinogenic, diet can alter the bacteria in the ecosystem and increase the risk of cancer. 'Westernised' high-fat diets were found to correlate with CRC.
- Influx of immune-stimulating microorganisms: Inflammation is a well-known driver in the development of cancer. Disruption of the epithelial layer (the thin tissue lining the colon) allows an influx of potentially harmful bacteria, increasing the potential to induce inflammation.
Throughout the review the research team discuss potential explanations for contrasting data but it is through further research that evidence of a causal relationship between the altered microbiota and host can be found.
"To uncover the desired clinical potential of the microbiome in CRC, we must continue to distinguish correlation and causation by systematically adding knowledge to the layers of complexity. Technological advances are providing tools to study the microbiota to accelerate progress and this, we hope, will help in the development of new therapeutics," said Alina.
Alina was funded by a Kennedy Trust for Rheumatology Research (KTRR) senior fellowship, which are offered annually by the Kennedy Institute to help to train the next generation of scientific leaders. This work was also highly supported by a Cancer Research UK (CRUK) grant and an MRC Experimental Medicine Grant.