Antibiotics Facilitate Intestinal C. difficile Colonization

A new study sheds light on the way antibiotics can promote C. difficile infections by killing beneficial bile-acid altering bacteria in the microbiota.

Researchers at North Carolina State University (NCSU; Raleigh, USA) and the University of Michigan (Ann Arbor, USA) used targeted bile acid metabolomics in order to define the physiologically relevant concentrations of primary and secondary bile acids present in murine small and large intestinal tracts, and how these bile acids impact C. difficile dynamics. To do so, they first identified 26 different primary and secondary bile acids, and defined the concentrations of those acids before treatment.

The mice were then treated with a variety of antibiotics to create distinct microbial and metabolic bile acid environments in order to test how they supported or inhibited spore germination and outgrowth. They found that the primary bile acids in the small intestine allow spores to germinate, regardless of antibiotic treatment. But when the spores reach the large intestine, secondary bile acids, produced mainly by Lachnospiraceae and Ruminococcaceae microbiota community members, successfully stop this germination.

However, when the beneficial bacteria and their secondary bile acids were not present due to antibiotic treatment, C. difficile spores were able to grow quickly. The susceptibility to C. difficile in the large intestine was observed only after specific broad-spectrum antibiotics (cefoperazone, clindamycin, and vancomycin), and was accompanied by a significant loss of the secondary bile acids deoxycholate, lithocholate, ursodeoxycholate, hyodeoxycholate, and ω-muricholate. The study was published in the January 2016 issue of mSphere.

“We know that within a healthy gut environment, the growth of C. diff is inhibited, but we wanted to learn more about the mechanisms behind that inhibitory effect. These findings are a first step in understanding how the gut microbiota regulates bile acids throughout the intestine,” said lead author assistant professor of infectious diseases Casey Theriot, PhD, of NCSU. “Hopefully, they will aid the development of future therapies for C. difficile infection and other metabolically relevant disorders, such as obesity and diabetes.”

C. difficile exists in the environment as a dormant spore. To colonize the gut, the spores need to germinate and turn in active, toxin-producing bacteria. Antibiotics that alter the gastrointestinal microbiota facilitate this germination, allowing infections to develop, resulting in a significant public health problem.

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North Carolina State University
University of Michigan