Why some people may be more susceptible to deadly C. difficile infections

An intestinal pathogen that causes severe and sometimes life-threatening diarrhea is an opportunist that grows like gangbusters under the right conditions. Now, scientists may have discovered the opportunity that Clostridioides difficile waits for.

In mice, a disruption of the mix of microbes in the gut sets the stage for C. difficile infections. Such upsets allow the pathogen to flourish partly by giving it more of the amino acid proline to eat, researchers report October 24 in Science Translational Medicine.

The U.S. Centers for Disease Control and Prevention estimated in 2015 that more than 148 in 1,000 people develop C. difficile (previously known as Clostridium difficile) infections. Such infections usually happen after people have taken antibiotics, which can throw off the usual mix of gut microbes.

Gastroenterologist Purna Kashyap of the Mayo Clinic in Rochester, Minn., and colleagues conducted experiments transplanting feces from people with normal or disturbed gut microbes into mice. Mice that got transplants from people with normal gut microbiomes were able to fight off or control C. difficile infections better than mice that got transplants from people with disturbed mixes.

Altered microbe mixes led to an increase in certain amino acids in the gut, particularly proline, the researchers found. C. difficile can use proline as its main food source, giving it a competitive advantage over microbes that don’t consume the amino acid as readily. Mice fed a proline-deficient mouse chow had much less C. difficile bacteria in their intestines as mice on a normal diet, the team found.

Fecal transplants were even more effective in keeping the mice’s C. difficile levels under control, says Kashyap. That suggests that probiotics containing other proline-eating bacteria might outcompete C. difficile and help restore the balance of gut microbes, he says.