Targeting certain bacterial strains linked to cancer with treatments or vaccines may help to reduce the risk of colorectal cancer, urothelial carcinoma, and prostate cancer, according to a novel study published by Mäklin et al in The Lancet Microbiome.
Background
The bacterium Escherichia coli is commonly found in the human gut. Most strains of E coli are harmless; however, if the bacterium gets into the bloodstream as a result of a weakened immune system, it can cause infections that range from mild to life-threatening.
Higher rates of certain cancer types in industrialized countries may be linked to dominant E coli strains producing a substance known as colibactin—which has previously been identified as a risk factor for colorectal cancer. The ability to produce colibactin is a rare feature of some E coli and is mainly found in two strains that have been estimated to be at least 300 hundred years old. These strains are not known to cause food poisoning.
Producing colibactin is energetically expensive for E coli and requires a genetic adaptations that ensure the process is not too costly for the bacteria. This adaptation is difficult to acquire by horizontal gene transfer, which is the way bacteria share traits. Consequently, only two successful E coli strains among the hundreds of E coli strains circulating globally have managed to establish a stable maintenance of the colibactin-producing genes during the past centuries.
Researchers have been using genomic surveillance to track strains of E coli across different countries, including the United Kingdom, Norway, Pakistan, and Bangladesh. This has allowed them to identify factors that could cause certain strains to spread and determine potential strategies to prevent disease-causing strains.
In 2020, a study revealed that colibactin can cause DNA breaks in human cells. They further found evidence of damage from colibactin in tumor samples from patients with colorectal cancer.
Study Methods and Results
In the recent study, researchers investigated the differences in cancer incidence for colorectal cancer, urothelial carcinoma, and prostate cancer. They then compared cancer incidence rates with global genomic surveillance data tracking E coli strains—specifically the two dominant E coli strains producing colibactin.
The researchers discovered that the two E coli strains are found more commonly in industrialized countries, where they may cause high rates of urinary tract and bloodstream infections. Industrialized countries also report higher rates of colorectal cancer, urothelial carcinoma, and prostate cancer. Comparatively, in countries with limited resources such as Bangladesh and Pakistan, the two colibactin-producing strains are much rarer, and incidences of these cancer types are also lower.
Higher rates of these cancer types in industrialized countries could be linked, in part, to the two E coli strains that produce colibactin. The researchers hypothesized that the geographic variation in cancer incidence may be affected by varying levels of population exposure to these two strains of E coli.
Therefore, interventions focused on eradicating these two E coli strains, such as with vaccines, may prevent them from circulating and, in turn, reduce the risk of certain types of cancers. Another avenue of treatment could be the development of therapeutic probiotic products that help displace the two E coli strains from the human gut, aiming to remove them from the population.
Because the strains are among the leading causes of urinary tract infections and bloodstream infections, an intervention to eliminate them would also reduce the infection burden and antibiotic use. Preliminary evidence has suggested that colibactin-producing E coli strains may play a role in the development of cancers of the urinary tract, including urothelial carcinoma and prostate cancer, since this is a common site of E coli infections.
“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. In the future, it could be possible to develop therapeutic probiotics that help to displace unwanted bacterial strains, such as the ones that release colibactin. 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,” stressed co–senior study author Trevor Lawley, PhD, of the Wellcome Sanger Institute.
Conclusions
“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. Having access to global genomic data on which strains are found in an area can uncover new trends and possibilities, such as strains in industrialized countries potentially being linked to the risk of certain cancers. We also need to keep ensuring that countries and regions around the world are included in genomic surveillance research, so everyone benefits from new discoveries,” highlighted lead study author Tommi Mäklin, MSc, PhD, of the University of Helsinki and the Wellcome Sanger Institute.
The researchers underlined that further large-scale investigations, including widespread tumor sampling, are needed to better understand the connection between the two E coli strains and the incidence of colorectal cancer, urothelial carcinoma, and prostate cancer as well as to clarify the role of colibactin in cancer.
“We have been using large-scale genomics to track E coli strains across multiple countries for the last 5 years, using data that goes back to the early 2000s. This has allowed us to start to see the possible connections between two E coli strains and cancer incidence rates. Science is not a stand-alone endeavor, 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,” underscored co–senior study author Jukka Corander, MSc, PhD, Professor at the University of Oslo, University of Helsinki, and Wellcome Sanger Institute. “Vaccines or other interventions that target these E coli strains could offer huge public health benefit [s]uch as reducing the burden of infections and lessening the need for antibiotics to treat these as well as reducing the risk of cancers that could be linked to the effects of colibactin exposure,” he concluded.
Disclosure: For full disclosures of the study authors, visit thelancet.com.
