Prostate cancer is the most common cancer among men in the UK. It accounts for more than a quarter of all new cases of cancer in men. In 2021, there were 49,385 new cases of bowel cancer, also known as colorectal cancer, in men and women. New research suggests that two particular strains of bacteria might provide the answer to reducing the risk of, and treating colorectal, bladder, and prostate cancers. However further investigation is needed.
Researchers from the Wellcome Sanger Institute, the University of Helsinki, and collaborators have investigated the differences in the incidence of these cancers across the world. Their paper, published in the Lancet Microbe, found that certain cancers were more common in industrialised countries. This could be linked, at least in part, to two Escherichia coli ( E.coli ) strains that produce colibactin, a substance previously identified as a risk factor for colorectal cancer.
Dr Trevor Lawley from the Wellcome Sanger Institute, said:
“Our guts contain many different types of bacteria, most of which are harmless, including some strains of E.coli. As not all bacterial strains can live in your gut at the same time, they have to compete for space and resources. Understanding more about the interactions between E.coli and cancer risk highlights the impact our microbiome has on our health and is a crucial avenue to explore if we want to work with our bodies to help combat certain conditions.”
E.coli and colibactin
The ability to produce colibactin is a rare feature of some E.coli strains. It is mainly only found in two strains that have been estimated to be at least 300 years old. The hope is that interventions that tackle these two strains, such as a vaccine or a probiotic, could prevent these bacterial strains from circulating, and in turn reduce cancer risk. Also, since these E.coli strains are the leading causes of urinary tract and bloodstream infections in industrialised countries, an intervention to eliminate them could also reduce these infections and allow antibiotic use to treat them.
In 2020, research found that colibactin causes DNA breaks in human cells. The team also found evidence of damage from colibactin in tumour samples from colorectal cancer patients.
Preliminary evidence suggests that colibactin-producing E.coli strains also play a role in the development of cancers of the urinary tract, such as bladder and prostate cancers.
Geographical variations
Researchers have studied how often certain cancers occur and compared this with detailed data about different types of E. coli bacteria.
In comparison to industrialised nations, the occurrence of the two colibactin-producing E.coli strains are much rarer in under-resourced countries such as Bangladesh and Pakistan. Incidences of bowel, bladder, and prostate cancers are also lower.
The theory by researchers is that the geographical variation in cancer occurrence is affected by varying levels of population exposure to these two strains of E. coli. Even so, further large-scale investigation is needed, including wide-spread tumour sampling, to clarify the role of colibactin in cancer.
Dr Tommi Mäklin, from the University of Helsinki and the Wellcome Sanger Institute, said:
“E. coli can be found around the world, in many different forms, and understanding how strains of this bacteria impact humans differently can give us a more complete picture of health and disease.”
Vaccines and treatments
Producing colibactin takes a lot of energy for E.coli and so requires a genetic adaptation that ensures the process is not too costly for the bacteria. This adaptation is hard for bacteria to pick up through the process they use to share traits with each other. As a result, only two successful E. coli strains, out of the hundreds of E. coli strains circulating globally, have managed to establish a stable maintenance of the colibactin producing genes.
Approaches aimed at eliminating the two E.coli strains, such as developing a vaccine, could be very effective. This could also help to reduce infections and lessen the need for antibiotics to treat them. Another avenue could be developing therapeutic probiotic products that help displace these two E.coli strains from the human gut, aiming to remove them from the population.
Professor Jukka Corander from the Wellcome Sanger Institute, University of Oslo and the University of Helsinki, said:
“Science is not a stand-alone endeavour and by working together with cancer and microbiome experts, we are hopeful that in the future this work might lead to new ways to eradicate colibactin-producing E. coli strains.
“Vaccines or other interventions that target these E.coli strains could offer huge public health benefits.”
This ground-breaking research marks an important step towards understanding how the bacteria in our guts influence cancer risk – and how we might harness that knowledge to save lives.
This research was funded in part by the Research Council of Norway, the Academy of Finland, and Wellcome.
A full acknowledgement list can be found in the publication.
