Protecting our microbiomes to boost cancer treatment results
The role of the microbes that make their homes in our intestine is a quickly developing area of research. One focus is on the relationship between certain bacteria and the progression of cancer along with the impact on treatment. Gut dysbiosis – an imbalance in the gut microbiota composition – has been associated with the staging and prognosis of cancer(opens in new window) within and beyond the intestine. Along with the development of tumours, certain species of gut bacteria have been shown to hamper the efficiency of a type of cancer immunotherapy which uses drugs to block proteins called checkpoints – known as immune checkpoint blockade (ICB). There is a growing interest in determining the microbial composition of a patient at baseline, to assess their propensity to benefit from ICB, or to determine their overall survival. “We wanted to validate cancer-associated, gut microbiome ‘fingerprints’ that could make a real difference for patients,” explains Laurence Zitvogel(opens in new window), who coordinated the ONCOBIOME(opens in new window) project. Hosted by the Gustave Roussy Institute(opens in new window) in France, the ONCOBIOME project set out to fully identify and characterise the ecosystems relevant to cancer, using reliable and robust methods.
Computing the ratio of beneficial and harmful bacteria in our gut
The field is a fast moving one. It is already possible to perform shotgun metagenomics analyses(opens in new window) of stool samples, as well as PCR testing(opens in new window) to trace bacteria that are beneficial or harmful for the host. “We can then compute a ratio between both, called a toposcore, to evaluate the risk of resistance to immunotherapy.” To improve our understanding of how our gut microbiome interacts with cancer, the team examined data arising from over 9 000 patients across 10 countries, covering 4 frequent cancer types: breast, colorectal, melanoma and lung. “We wanted to identify and validate cancer-specific Gut OncoMicrobiome Signatures (GOMSs) associated with cancer occurrence, prognosis and response to therapy. And then to integrate these GOMSs with other oncology hallmarks to design tests to predict cancer occurrence and progression,” says Zitvogel.
Designing cancer tests around Gut OncoMicrobiome Signatures
ONCOBIOME ran studies testing the impact of medications, such as benzodiazepines and antibiotics, on the microbiome along with the impact of lifestyle and diet. They diagnosed gut dysbiosis by using stool and serum specimens. Prospective validation of these diagnostic tests is being currently achieved in close collaboration with biotechnological companies working with different hospitals in Europe. Prebiotics such as camu-camu(opens in new window) and castalagin(opens in new window), and probiotics such as lyophilised encapsulated Clostridium butyricum and Akkermansia massiliensis, are being developed. Randomised Phase II studies with live biotherapeutics and faecal microbial transplantation are conducted in Canada, Italy and France among other sites. “The ultimate aim is to address the problem of gut dysbiosis by reducing the over-prescription of drugs which negatively impact on the gut microbiota. Changing diet can be key too, as is taking live biotherapeutics. Faecal microbial transplantation, in case of severe dysbiosis, can also play an important role right before starting cancer immunotherapy. “These interceptive manoeuvres are being developed at several cancer centres in randomised trials,” Zitvogel explains.
A new approach to the treatment of cancer
Projects such as ONCOBIOME are showing that a healthy intestinal barrier and a balanced microbiome working together, is necessary for our bodily fitness and our ability to fully respond to anticancer immunotherapies. “A novel era is born,” adds Zitvogel: “No one can ignore the ‘whole-body’, ecological view of cancer.”
