Recent advancements in the exploitation of the gut microbiome in the diagnosis and treatment of colorectal cancer

Abstract

Over the last few decades it has been established that the complex interaction between the host and the multitude of organisms that compose the intestinal microbiota plays an important role in human metabolic health and disease. Whilst there is no defined consensus on the composition of a healthy microbiome due to confounding factors such as ethnicity, geographical locations, age and sex, there are undoubtably populations of microbes that are consistently dysregulated in gut diseases including colorectal cancer (CRC). In this review, we discuss the most recent advances in the application of the gut microbiota, not just bacteria, and derived microbial compounds in the diagnosis of CRC and the potential to exploit microbes as novel agents in the management and treatment of CRC. We highlight examples of the microbiota, and their derivatives, that have the potential to become standalone diagnostic tools or be used in combination with current screening techniques to improve sensitivity and specificity for earlier CRC diagnoses and provide a perspective on their potential as biotherapeutics with translatability to clinical trials.

Keywords: bacterio-thearpy; colorectal cancer; diagnostic biomarkers; intestine; microbiome.

Figure 1. Schematic representation of the transitioning role of the gut microbiota from healthy to diseased states with examples of microbial changes and diagnostics techniques

Figure 2. Harnessing the microbiome as therapeutic tools in the treatment of solid cancers

The involvement of the gut microbiome and pathogenic bacteria in the development of cancer has been previously documented. Novel therapeutics strategies are being developed to modify the gut microbiome to aid cancer treatment. The gut microbiome can be modified through alteration to a person’s diet and lifestyle, the administration of probiotics, faecal microbiota transplantation or antibiotic therapies. More recently the use of targeted modulation using bacteria has emerged, known as bacteriotherapy. Importantly attenuated bacteria that specifically target the tumour are used to initiate an immune response without the undesirable toxicities usually associated with the bacterium. Such bacteria are often also genetically modified to improve their tumour targeting ability and to deliver various biomolecules, prodrug-converting enzymes or toxins to promote cancer cell death. Often clinical trials exploit multiples arms of these microbial therapies to improve tumour treatment and as such this highlights the flexibility of these therapeutic approaches.