Colorectal cancer and the microbiome: Some interesting links!

Over the years, researchers have identified the major risk factors for developing CRC. Apart from genetic considerations, a number of dietary and lifestyle factors[2] are also involved:

• Sedentary lifestyle, lack of exercise, excess weight and obesity
• Consuming alcohol and tobacco
• A diet rich in red and processed meats and/or low in fibre
• Eating foods cooked at a high temperature
• Inflammatory bowel disease (such as Crohn’s disease or ulcerative colitis)
• Diabetes

The word “microbiome” does not appear in this list. However, over the past decade, numerous studies have identified close links between many of these risk factors and the health of our microbiome, and consequently, the development of colorectal cancer.

The microbiome, also known as the microbiota, refers to all the microorganisms, including bacteria, viruses, moulds and their genetic material that normally live in our bodies, especially in the digestive tract. In the human body, there are just as many microbial organisms as there are human cells, underscoring the crucial importance of the microbiome to our health. Its diversity is remarkable: For bacteria alone, there are more than 1,000 different species in the body of a normal human, not counting viruses, moulds and all the interactions between these various microorganisms.[3] The composition of the intestinal microbiome forms progressively in the newborn, first through contact with the mother’s vaginal and fecal flora during vaginal delivery, or with microorganisms in the atmosphere during a caesarean delivery. It then develops through the influence of diet, genetics, hygiene, the environment and certain treatments such as antibiotics.[4] Although many types of microorganisms are found in most human beings, the differences between individuals are so great that the microbiome is sometimes compared to a fingerprint.[4]

Among the many factors known to alter the microbiome (genetic, dietary and others), several are also found in the list of risk factors for colorectal cancer.

• Obesity can alter the composition of the microbiome.
• Inflammatory bowel disease can lead to an inadequate activation of the immune response in the gut.
• Physical exercise can increase the diversity and proportion of good bacteria.[5]
• Eating red meats can lead to an increase in harmful bacteria and the secretion of toxins.[6]
• Alcohol consumption can alter the composition of the microbiome and lead to the secretion of endotoxins.[7]

As such, it is not surprising that changes in the microbiome (dysbiosis) are now considered a significant, even pivotal, risk factor for the development of colorectal cancer.[8]

The relationship between microbiome composition and CRC risk is so close that some researchers believe an analysis of microbiome composition could predict the risk of developing CRC with good certainty.[9,10] However, this complex analysis is not yet sufficiently developed for use in medicine.

Last year, a group of researchers at the CHUM published a study. In mice, altering the microbiome before intestinal surgery was found to reduce post-operative complications in patients with CRC.[11] Accordingly, by modifying the mouse’s microbiome to reduce the amount of harmful bacteria and increase the amount of useful bacteria, the researchers observed an improvement in intestinal healing. However, in reality, almost one in three patients undergoing CRC surgery develops serious post-operative complications linked to leakage caused by poor healing of the intestinal barrier. These complications take the form of inflammation, severe infection or recurrence of the cancer. The researchers were able to identify more specifically a strain of bacteria responsible for these leaks, as well as another strain of bacteria which, on the contrary, promotes healing.

These results are promising in a field where research is currently scarce.[12] The technique used in mice involved “transplanting” feces from an animal that had healed well after surgery to another mouse prior to its own surgery. This fecal transplant (FMT) approach is less straightforward in humans, although the technique is already used to treat recurrent C. difficile infections.[13] It is easier to find a human donor uninfected with C. difficile than to find a donor with the right proportion of beneficial and harmful bacteria. Moreover, a great deal of research is still needed to determine the right mix of prebiotics and probiotics that will be effective in the majority of patients.

The “diagnosis” of CRC is officially established in the report of the pathologist who examines tissue removed by biopsy (during colonoscopy or surgery) under the microscope. Screening for CRC, on the other hand, aims to identify, within a large population, people who are at increased risk of developing CRC before the onset of specific symptoms, thereby justifying a colonoscopy. To be effective, a screening program must be based on the use of a simple, yet sensitive, inexpensive and easily available technique. Only people who are at high risk, or who have had a positive result in a screening test, are referred for more invasive, costly and less readily available examinations.

When colorectal cancer is diagnosed, the patient meets with the care team to discuss the treatment. This may involve surgery, chemotherapy or a combination of both, depending on the location of the tumour, where the cancer has reappeared (in the event of recurrence), the stage of the cancer, as well as the patient’s overall health condition and choice.

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