The gut microbiome is influential on the progression of health, perhaps to a similar degree as regular moderate exercise. Age-related changes in these microbial populations can promote chronic inflammation and tissue dysfunction, though the direction of causation is still up for debate when it comes to many of the details of the relationship between tissue and immune issues in the intestine and an altered gut microbiome. Nonetheless, less desirable microbes undertake activities that can raise the risk of cancer resulting from inflammation of the intestines, occurring in conditions such as inflammatory bowel disease. Researchers here demonstrate that suitable adjustment of microbial populations in mice can lower the incidence of cancer in this circumstance. This is one application among what will no doubt be many cases in which the gut microbiome can be shifted in ways that promote better health over the long term.
People living with inflammatory bowel disease (IBD) have a three- to sevenfold higher risk of developing colon cancer. Researchers have now shown that precision editing of the bacterial populations in the gut reduces inflammation-associated colorectal cancer in mice. "The most significant finding in this study is that manipulating the intestinal microbiome is sufficient to affect the development of tumors. One could envision a time in which medications that change the behavior and composition of the bacteria that live in the gut will be part of the treatment for IBD."
In addition to colorectal cancer, long-standing IBD is associated with imbalances in the bacterial species that line the gut. "Our intestinal tract is teeming with microbes, many of which are beneficial and contribute to our overall health. Yet, under certain conditions, the normal function of these microbial communities can be disturbed. An overabundance of certain microbes is associated with increased risk for the development of diseases, including certain cancers." The strategy used in the study targets metabolic pathways that are only active during intestinal inflammation and only in some forms of bacteria, providing an Achilles' heel for reducing their abundance. The current study builds on work that found the approach prevented or reduced inflammation in a mouse model of colitis, while having no obvious effect on healthy control animals with balanced bacterial populations in their guts.
"For example, most E. coli bacteria are harmless and protect the human gut from other intestinal pathogens such as Salmonella, a common cause of food poisoning. However, a subset of E. coli bacteria produce a toxin that induces DNA damage and can cause colon cancer in research animals. We developed a simple approach - giving a water-soluble tungsten salt to mice genetically predisposed to develop inflammation - to change the way potentially harmful E. coli bacteria generate energy for growth. Restricting the growth of these bacteria decreased intestinal inflammation and reduced the incidence of tumors in two models of colorectal cancer. Tungsten is a heavy metal and should not be used by anyone due to its toxicity. This is a proof-of-concept study that will guide us in developing future drugs with similar activity and less toxicity."