GEN Exclusives

More »

GEN News Highlights

More »
Aug 17, 2012

Gut Bug Links Inflammation to Colorectal Cancer

  • A genetic variant of E. coli may represent the causal bridge that connects intestinal inflammation with the development of bowel cancer, researchers claim. It’s already known that chronic gut inflammation disturbs the balance of microbes that naturally inhabit the digestive tract, and that patients with inflammatory gut disorders are more likely to develop bowel cancer. Studies in mice and humans now indicate that colorectal cancer is more likely to develop when this inflammation-related imbalance in microbiota is associated with the emergence of populations of an E. coli strain carrying a gene set known as the pks island.

    The findings are reported in Science, by an international team led by investigators at the University of North Carolina at Chapel Hill. Christian Jobin, Ph.D., and colleagues looked at the changes in gut microbe populations in a colitis-prone mouse model that lacks the gene for IL10, an interleukin that suppresses the inflammatory response. They found that intestinal inflammation in these animals led to a disturbance of the intestinal ecosystem and far lower diversity of bacterial inhabitants, but relatively much larger populations of E. coli. When they then infected the IL10-knockout mice that had been raised under sterile conditions with either an E. coli variant known as NC101, or with another common gut bacterium, Enterococcus faecalis, both groups developed severe gut inflammation, but 80% of the E. coli-infected animals also went on to develop tumors.

    In contrast, tumor development didn’t occur in the Enterococcus faecalis-infected mice. “This would argue pretty strongly that there’s something in the E. coli that’s causing the mice to develop cancer,” comments co-author Anthony Fodor, Ph.D., an associate professor of bioinformatics at the University of North Carolina at Charlotte.

    To try and find out what it was in the E. coli that was triggering cancer development, the authors looked more closely at the genetic makeup of the bacteria, and in particular the pks island gene set carried by some strains of E. coli that has been implicated in causing DNA damage. Critically, when they infected the experimental mice with an NC101 E. coli strain that lacked the pks island, the animals still developed inflammation, but exhibited a markedly lower rate of tumor formation. And when they compared bacteria colonizing healthy people, those with irritable bowel syndrome, and patients with colorectal cancer, they found pks-carrying E. coli in two thirds of colorectal cancer patients, but a much lower proportion of those with IBS (40%), and in even fewer healthy controls (20%).

    "These are exciting results because they suggest there may be a direct link between changes in the gut microbiome and the progression from inflammation to cancer," Dr. Fodor concludes. "If we can understand the pathways by which pathogens damage host cells within the context of host inflammation, we may be able to formulate a personalized approach to cancer prevention in which particular pathogenic taxa or genes are targeted in vulnerable human subpopulations."

    Drs. Fodor, Jobin, et al report their findings in a paper titled “Intestinal Inflammation Targets Cancer-Inducing Activity of the Microbiota.”


Add a comment

  • You must be signed in to perform this action.
    Click here to Login or Register for free.
    You will be taken back to your selected item after Login/Registration.

Related content

Jobs

GEN Jobs powered by HireLifeScience.com connects you directly to employers in pharma, biotech, and the life sciences. View 40 to 50 fresh job postings daily or search for employment opportunities including those in R&D, clinical research, QA/QC, biomanufacturing, and regulatory affairs.
 Searching...
More »

GEN Poll

More » Poll Results »

Alzheimer's Therapies

Do you think an effective treatment for Alzheimer’s will be found within the next 10–15 years?