Today, we want to highlight a recent study in which a team of researchers from UT Southwestern demonstrates how adjusting the gut microbiome in mice lowers the occurrence of cancer.
What is the gut microbiome?
The microbiome describes a varied community of bacteria, archaea, eukarya, and viruses that inhabit our gut. The four bacterial phyla of Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria make up around 98% of the intestinal microbiome.
The microbiome community is essentially a complex ecosystem whose activity regulates a number of functions in the gut and interacts with the immune system and energy metabolism. The beneficial bacteria in our guts also help to prevent the growth of harmful bacteria, protect us from invasive microorganisms, and maintain the integrity of the intestinal barrier.
Unfortunately, as we age, the diversity and numbers of beneficial bacteria in the microbiome start to fall, and this is thought to contribute to aging, particularly for its role in the chronic age-related inflammation known as inflammaging.
Changes to the microbiome and the resulting inflammation are also believed to facilitate a number of age-related diseases, and the changes to the microbiome can raise the risk of cancer via intestinal inflammatory conditions, such as inflammatory bowel disease.
Targeting harmful bacteria to reduce cancer risk
The new study demonstrates that adjustments to the gut microbiome can be made and, in doing so, can reduce the chance of developing cancer, at least at this point in time, in mice. This research builds on the growing appreciation for how the microbiome is important in health and that adjusting it may allow us to maintain health as we get older.
The study was focused on inflammatory bowel disease (IBD), which is thought to affect around 1.6 million people in the United States alone and is associated with adverse changes to the populations of bacteria that line the gut. People with IBD have a greater risk of developing colorectal cancer, which, according to the World Health Organization, is the third most common type of cancer globally. IBD is thought to increase the risk of colorectal cancer up to sevenfold.
The researchers used an approach that targeted pathways associated with intestinal inflammation created only by specific strains of bacteria, so they were able to reduce the harmful bacteria without affecting the populations of beneficial ones. For example, E. coli (Escherichia coli) bacteria are generally harmless and actually protect the gut from pathogens such as salmonella; however, animal studies have shown that one particular harmful strain of E. coli secretes a toxin that causes DNA damage and supports the development of colon cancer.
The researchers chose a breed of mice genetically predisposed to experience inflammation and treated them with water-soluble tungsten salt, which affects how this E. coli strain produces energy and, therefore, how it is able to grow and reproduce. The salt was able to inhibit the growth of the target bacteria, decrease intestinal inflammation, and reduce the occurrence of tumors in two mouse models of colorectal cancer.
Chronic inflammation and gut microbiota dysbiosis, in particular the bloom of genotoxin-producing E. coli strains, are risk factors for the development of colorectal cancer. Here, we sought to determine whether precision editing of gut microbiota metabolism and composition could decrease the risk for tumor development in mouse models of colitis-associated colorectal cancer (CAC). Expansion of experimentally introduced E. coli strains in the azoxymethane/dextran sulfate sodium colitis model was driven by molybdoenzyme-dependent metabolic pathways. Oral administration of sodium tungstate inhibited E. coli molybdoenzymes and selectively decreased gut colonization with genotoxin-producing E. coli and other Enterobacteriaceae. Restricting the bloom of Enterobacteriaceae decreased intestinal inflammation and reduced the incidence of colonic tumors in two models of CAC, the azoxymethane/dextran sulfate sodium colitis model and azoxymethane-treated, Il10-deficient mice. We conclude that metabolic targeting of protumoral Enterobacteriaceae during chronic inflammation is a suitable strategy to prevent the development of malignancies arising from gut microbiota dysbiosis.
The role of the gut microbiome and health and aging is starting to become truly appreciated, and, as this study shows, can have a dramatic influence on health and risk of disease.
A final word of caution: tungsten is a heavy metal and should not be taken due to its toxicity. The study is a proof-of-concept for the approach of targeting harmful populations of gut bacteria in order to improve health, and the researchers are now working to develop drugs that target the same bacteria but without the toxicity that tungsten salt has. In other words, please don’t try this at home, or you will give yourself heavy metal poisoning!
 Zhu, W., Miyata, N., Winter, M. G., Arenales, A., Hughes, E. R., Spiga, L., … & Byndloss, M. X. (2019). Editing of the gut microbiota reduces carcinogenesis in mouse models of colitis-associated colorectal cancer. Journal of Experimental Medicine, jem-20181939.