Breakthrough Discovery: Bacteria Reveal Promising Target for Colon Cancer Vaccine

Researchers from the Wellcome Sanger Institute, the University of Helsinki, and their partners examined the rates of colorectal, bladder, and prostate cancers, comparing these statistics to global data on Escherichia coli (E.coli) strains. They specifically focused on the two dominant E.coli strains that produce a substance previously recognized as a colorectal cancer risk factor.

In their study published in the Lancet Microbe, they noted that these E.coli strains are more prevalent in developed nations, where they lead to high occurrences of urinary tract infections (UTIs) and bloodstream infections, without causing food poisoning.

The researchers propose that the rise in certain cancer rates in these countries could partially relate to the two identified E.coli strains that generate a substance called colibactin, while emphasizing the need for further research.

The production of colibactin is uncommon for E.coli, primarily found in just two strains believed to be at least 300 years old. Therefore, interventions targeting these two strains, such as vaccines or probiotics, might prevent their spread and thus lower cancer risks.

Additionally, since these E.coli strains are leading causes of UTIs and bloodstream infections in developed nations, efforts to eliminate them would also alleviate the infection burden and reduce antibiotic consumption.

E. coli typically resides in the human intestines. The majority of its strains are benign; however, if they enter the bloodstream—especially in individuals with weakened immune systems—they can trigger infections that range from mild to severe.

Researchers, including members of this team, have been employing genomic surveillance to monitor various E.coli strains across nations, including the UK, Norway, Pakistan, and Bangladesh. This monitoring helps in identifying factors that facilitate the spread of specific strains and in discovering new potential methods to combat disease-causing strains.¹

In 2020, studies revealed that colibactin—a substance produced by certain bacteria, including two E.coli strains—can cause DNA damage in human cells. The research team also found signs of colibactin damage in tumor samples from colorectal cancer patients.²

Preliminary findings indicate that colibactin-producing E.coli strains might also be involved in developing urinary tract cancers, such as bladder and prostate cancers, as these areas are common sites for E.coli infections.^3,4

In this study, the researchers compared cancer incidence rates with genomic data on E.coli. They discovered that the colibactin-producing E.coli strains are more common in developed nations that also report higher rates of bowel, bladder, and prostate cancers.

In contrast, under-resourced nations like Bangladesh and Pakistan have much lower occurrences of these two colibactin-producing strains and consequently report fewer cases of bowel, bladder, and prostate cancers.

The team theorizes that geographical differences in cancer rates may stem from varying levels of population exposure to these E. coli strains. However, substantial further research, including extensive tumor sampling, is essential to clarify colibactin’s role in cancer development.

Producing colibactin is energetically demanding for E.coli and requires specific genetic adaptations to ensure the process does not incur excessive costs for the bacteria. This adaptation is challenging to achieve through horizontal gene transfer—the method by which bacteria share characteristics. Consequently, only two successful E.coli strains have managed to maintain their colibactin-producing genes over centuries.

As a result, interventions aimed at eradicating these two strains, such as vaccines, could be very effective. Another potential approach could involve creating therapeutic probiotic products to help replace these two E.coli strains in the human gut, effectively removing them from circulation.

Dr. Tommi Mäklin, the study’s first author from the University of Helsinki and the Wellcome Sanger Institute, stated: “E. coli exists globally in various forms, and understanding how these strains affect humans differently enhances our knowledge of health and disease. Access to global genomic data on local strains can reveal new trends and possibilities, such as the potential connection between strains in developed countries and certain cancer risks. It is vital to ensure that genomic surveillance research includes diverse countries and regions for collective benefit from new findings.”

Dr. Trevor Lawley, a senior author from the Wellcome Sanger Institute, added: “Our intestines host numerous bacterial types, most of which are harmless, including some E.coli strains. Since not all strains can coexist in the gut simultaneously, competition for space and resources occurs. In the future, therapeutic probiotics might help displace undesirable bacterial strains, including those that produce colibactin. Gaining more insight into E.coli‘s interactions with cancer risk underscores the microbiome’s influence on our health, an important area to explore to support our bodies in combating specific conditions.”

Professor Jukka Corander, a senior author from the Wellcome Sanger Institute, the University of Oslo, and the University of Helsinki, mentioned: “For the past five years, we have been utilizing large-scale genomics to trace E. coli strains across several countries, using data dating back to the early 2000s. This has enabled us to start establishing potential links between two E.coli strains and cancer rates. Science thrives on collaboration; by working alongside cancer and microbiome specialists, we are hopeful that this research will lead to effective methods for eradicating colibactin-producing E. coli strains in the future. Targeted vaccines or other interventions could significantly improve public health by reducing infection rates and lessening the reliance on antibiotics, as well as lowering cancer risks associated with colibactin exposure.”