Body’s defense against microbes may become counterproductive in the gut
Inflamed intestines produce their own brand of fertilizers, which nourish E. coli and other disease-associated bacteria, a new study shows.
Everyone carries a small amount of E. coli in their intestines, and it normally causes no problems. But compared with people who have healthy colons, people with inflammatory bowel diseases such as ulcerative colitis or Crohn’s disease harbor a mix of intestinal microbes that is heavier on E. coli.
No one knew whether the disease or the altered microbial mix came first. The new study, published in the Feb. 8 Science, takes a step toward unraveling that chicken-or-egg tangle. Inflammation, a process the body usually uses to kill microbes, may instead feed “bad” bacteria, further inflaming the gut.
Scientists know that during inflammation, tissues produce chemicals such as nitric oxide and superoxides, which can break DNA and ravage bacterial cells. But in experiments involving mice, Andreas Bäumler of the University of California, Davis and colleagues discovered that when the chemicals react with each other, they can produce nitrates and other compounds that some bacteria use for fuel.
The analysis suggests that some bacteria take advantage of changes in a host’s metabolism to overcome competitors, says David Low, a microbial geneticist at the University of California, Santa Barbara. Understanding how the bacteria do this may eventually lead to new therapies or preventative strategies.
E. coli normally makes up a tiny fraction — usually about 0.1 percent — of the bacteria in the gut, Bäumler says. In an inflamed colon, the bacteria can bloom to about 10 percent of the intestinal microbe mix, crowding out friendlier types.
To find out how E. coli and related bacteria accomplish the takeover, Bäumler and his colleagues inflamed mice’s bowels by injecting a chemical irritant. They found that inflamed colons, but not healthy ones, produce nitrate.
Scientists know that most bacteria in the gut aren’t equipped to consume nitrate. But E. coli and related bacteria can. These bacteria contain enzymes that use nitrate and other chemicals to produce energy. That gives them a food source other bacteria can’t use.
Bacteria fight vigorously over nutrients in the colon, Bäumler says. “If you can sidestep the competition, you have a huge advantage.” His team found that mutant E. coli strains that can’t use nitrate for food also can’t outcompete normal bacteria.
Inflammation is essential to E. coli’s colon-domination strategy, the researchers found. Mice with normal colons didn’t experience E. coli overgrowth. Blocking an enzyme that produces nitric oxide, nitrate’s precursor, in intestinal cells also stopped the E. coli incursion in inflamed guts, the researchers found.
Taken together, the results suggest that removing inflammation-generated nitrate or blocking E. coli’s ability to use it could limit the bacterium’s growth in the intestines. But nitric oxide plays important roles throughout the body such as regulating blood vessel dilation, so disabling the enzyme that produces it may not represent a good strategy for treating bowel diseases.
“You can’t just take a sledgehammer and knock out something like that without having a lot of other repercussions,” Low says.Bäumler says his group is working on potential treatments that would restore the normal microbial mix by preventing E. coli and related bacteria from using the nitrate.
S. E. Winter et al. Host-derived nitrate boosts growth of E. coli in the inflamed gut. Science, Vol. 339, February 8, 2013, p. 708. doi: 10.1126/science.1232467
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