Mouse study finds clear linkages between inflammation, bacterial communities and cancer
Posted by Xeno on August 21, 2012
What if a key factor ultimately behind a cancer was not a genetic defect but ecological? Ecologists have long known that when some major change disturbs an environment in some way, ecosystem structure is likely to change dramatically. Further, this shift in interconnected species’ diversity, abundances, and relationships can in turn have a transforming effect on health of the whole landscape — causing a rich woodland or grassland to become permanently degraded, for example — as the ecosystem becomes unstable and then breaks down the environment.
For this reason, it should come as no surprise that a significant disturbance in the human body can profoundly alter the makeup of otherwise stable microbial communities co-existing within it and that changes in the internal ecology known as the human microbiome can result in unexpected and drastic consequences for human health.
A report published in the August 16 online edition of the journal Science gives evidence for such a chain reaction. It has long been known that gut inflammation is a risk factor for cancer. The new study suggests that this may be in part because inflammation disturbs gut ecosystems leading to conditions that allow pathogens to invade the gut. These pathogens may damage host cells increasing the risk of the development of colorectal cancer.
The authors of the study were Janelle C. Arthur, Ernesto Perez-Chanona, Marcus Mühlbauer, Sarah Tomkovich, Joshua M. Uronis, Ting-Jia Fan, Christian Jobin, Arlin B. Rogers, Jonathan J. Hansen, and Temitope O. Keku from the University of North Carolina at Chapel Hill; Barry J. Campbell and Jonathan M. Rhodes from the University of Liverpool; Turki Abujamel and Alain Stintzi from the University of Ottawa; Belgin Dogan and Kenneth W. Simpson from Cornell University; and Anthony A. Fodor from the University of North Carolina at Charlotte.
In a series of experiments conducted with mice prone to intestinal inflammation, the researchers found that inflammation itself causes significant simplification in diverse communities of gut microbes and allows new bacterial populations to establish major footholds. Among the bacterial taxa invading the disturbed intestinal ecosystem, the research team found a greatly increased presence of E. coli and related bacteria. By putting E. coli bacteria into mice that were raised under sterile conditions, the team also found that the presence of E. coli promoted tumor formation. When regions of the E. coli genome known to be involved in DNA damage were removed, the ability of the E. coli to cause tumors was substantially decreased. …
From reviewing the literature on E. coli and associated bacteria, the researchers knew that some strains of E. coli contain a set of genes known as “the pks island” that have been implicated in pathways that cause DNA damage. Remarkably, the researchers found that when mice were inoculated with a modified NC101 E. coli in which the pks island had been removed, the mice still developed inflammation but had a dramatically reduced rate of tumor formation. The researchers concluded that the host-microbial interactions that allow E. coli to cause inflammation are distinct from the interactions that cause that inflammation to progress to cancer.
The team then looked to human subjects to see if there was a specific association of pks-containing bacteria with colorectal cancer. The team examined 24 healthy people, 35 with irritable bowel disease (which includes gut inflammation) and 21 with colorectal cancer.
“Remarkably, we found the bug with pks in only 5 out of 24 controls (20% in healthy people), but if you look at people with inflammatory bowel disease, the bug and pks were present in 14 out of 35 (40%,) and with people with colorectal cancer it was 15 out of 21 (66.7%),” Fodor noted.
“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,” said Fodor. “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 sub-populations.” …
I’ve started eating and learning to make my own raw sauerkraut. Smells terrible unless you use enough salt to inhibit the bad bacteria. Here’s a recipe similar to mine.