Precision editing of gut bacteria reduces cancer in mice

Precision editing of gut bacteria reduces cancer in mice


Researchers have shown that precision editing of the bacterial populations in the gut reduces inflammation-associated colorectal cancer in mice.

The study published by the Journal of Experimental Medicine. IBD increases the risk of colorectal cancer by three- to sevenfold. Because of that association, patients with persistent bowel inflammation should get intestinal screening, called colonoscopy, three to 10 times more often than healthy people who have no family history of such cancer: every one to three years vs. every 10, co-corresponding author said.

"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," the author added.

In addition to colorectal cancer, long-standing IBD is associated with imbalances in the bacterial species that line the gut, explained the other co-corresponding author.

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 the researchers published last year in Nature 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 (Escherichia 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," the author said.

"Tungsten is a heavy metal and should not be used by anyone due to its toxicity," the author added. "As with our 2018 paper, this is a proof-of-concept study that will guide us in developing future drugs with similar activity and less toxicity."

Precision editing of the gut microbiome is a shift in strategy from current clinical treatments that target reducing inflammation in the patient during IBD flare-ups or using broad-spectrum antibiotics that kill both good and bad bacteria in order to reduce the risk of cancer, the researchers said.

"Here, we present evidence that targeting the gut microbiota can be sufficient to affect tumor formation in a significant and meaningful way," the author said.

https://www.utsouthwestern.edu/newsroom/articles/year-2019/precision-editing-gut-bacteria.html

http://jem.rupress.org/content/early/2019/07/26/jem.20181939

Edited

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