Gastrointestinal bobbins used to connect pieces of the colon and create anastomoses
Often times when people undergo colon surgeries the colon must be re-adjoined, creating what is called an anastomosis. Around 50% of the time this anastomosis will not heal properly, and bacteria can escape from the gut into the body. Even with improvements to surgical techniques the rates for anastomotic leak have not really improved over the years. In fact, due to the likelihood of a patient developing this sometimes-deadly ailment, many surgeons will not even attempt to re-adjoin a colon, and instead just create a stoma (i.e. divert the colon outside the body). It has been known that bacteria somehow cause anastomotic leaks, so intravenous antibiotics are given as standard care, but they have not been highly effective because the mechanism behind the bacterial involvement is still unknown. However, a big step forward in elucidating the microbiome’s contribution to this disease was made by a group out of the University of Chicago. They recently discovered that common gut bacteria, Enterococcus faecalis and Proteus mirabilis, actually hinder the bodies natural wound repair process. They published their results in the Science Translational Medicine last week.
First, the scientists performed a colon resection on mice and then tracked which ones developed anastomotic leaks and which ones healed normally. Eventually they sacrificed the animals and made a number of measurements on the resectioned colons, which allowed them to compare the results between the groups. The first thing they discovered was that enzymes responsible for degrading collagen were much higher in mice that had the leaky anastomoses. (Collagen a molecule produced by the body that is important to reattaching the sections.) Next, they cultured organisms that were taken from the sites of the anastomoses and measured their ability to degrade collagen. They found that two members of the communities, Enterococcus faecalis, and Proteus mirabilis, had the highest collagen degradation activity. Interestingly, only some strains of E. faecalis had high collagen degradation activity, and it was these exact strains that were found in the leaky anastomoses, whereas the healthy anastomoses contained the other, non-collagen degrading, E. faecalis. Moreover, when the researchers transplanted these virulent strains of E. faecalis into the guts of mice that just underwent colon sectioning these mice developed leaky anastomoses regardless of whether or not they were given antibiotics intravenously. However, when antibiotics were applied directly to the anastomoses and E. faecalis was not able to grow, leakiness did not develop. In a final experiment the researchers cultured bacteria from humans that had just undergone colon surgery and discovered that their anastomoses contained E. faecalis and other collagen degrading bacteria (although only one developed anostomatic leak).
The researchers actually went a step further and pinpointed the actual genes that were associated with degrading the collagen, and I leave it to our most interested viewers to read the paper and find out more. Thanks to research like this, and better, more targeted antibiotics, doctors are a step closer to curing leaky anastomoses.