Posts Tagged ‘microbial communities’

Research Finds Link Between Inflammation, Bacterial Communities and Cancer.

Friday, August 24th, 2012

A new study published online in the journal Science concluded that a significant disturbance in the human body can profoundly alter the makeup of an otherwise stable microbial community coexisting within it and that changes in the internal ecology can result in unexpected and drastic consequences for human health. In a series of experiments using mice prone to intestinal inflammation the researchers found that inflammation caused simplification in diverse communities of gut microbes and allowed a new bacterial population  to establish a foothold. These pathogens then may damage host cells increasing the risk of developing colorectal cancer. Bacteria taxa often invading the disturbed intestinal ecosystem were E.Coli and related bacteria. By putting E. coli bacteria in mice raised in a sterile environment the researchers found that the presence of  E. coli promoted  tumor formation but when the region of the E. coli genome responsible for DNA damage was removed the ability of the E. coli to cause tumors was significantly decreased.  Researchers also found an E. coli variant with the suspected genes in a high percentage of human patients with colorectal cancer and irritable bowel disease.

There first study looked at determining a clear connection between the physiological condition of intestinal inflammation and a subsequent change in microbial communities in the gut. They used mice that are genetically prone to inflammation because they lack the gene that suppresses the inflammation response. The researchers compared bacterial communities in the inflamed gut of this group of mice with those bacteria  in healthy field mice. They found the diversity of different kinds of bacteria was lower in the mice with genetically facilitated inflammation but there was little difference in the microbial diversity between those that had inflammation and those that had cancer and this indicated that inflammation was the critical factor affecting microbe populations. They said ” A shift in the microbial community is associated with inflammation.” “It is interesting that the microbial community is actually  changing with the disease state, which indicates that it is either responding to or contributing to the disease state.”

Next they studied whether or not there was a relationship between E. coli and colorectal cancer. For this they raised sterile (bacteria free) mice that were genetically prone to inflammation  and inoculated each mouse with either E. coli variant (NC lOl) or Enterococcus faecalis, another common gut bacteria.  Both groups of the inflammation prone mice developed severe gut inflammation (colitis) but of significance, 80 percent of the E. coli infected mice also developed cxolorectal cancer, while the other group remained cancer-free. The researchers said it was the presence of the  E. coli in an inflammed environment that lead to the cancer rather than the inflammation itself.

Next they wanted to know what was it in the E. coli that caused cancer. Knowing that some strains of E.coli have a set of genes known as “the pks island” that have been implicated in pathways causing DNA damage, they innoculated mice with a modified NC lOl  E. coli that lacked the pks island and the mice still developed inflammation but  had a dramatically  reduced rate of tumors. Researchers concluded that host-microbial interactions that allow E. coli to cause inflammation are distinct from the interactions that cause the inflammation to progress to cancer.

Their next step was to look at human subjects to see if there was an association of pks containing bacteria with colorectal cancer. Subjects included 24 healthy people, 35 people with irritable bowel disease (including inflammation) , and 21 with colorectal cancer.  Researchers said “Remarkably, we found the bug with pks in only 5 out of 24 controls (29% 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%).”  “These are exciting results because they suggest there may be a direct link between changes in tyhe gut microbiome and the progression from inflammation to cancer.”