Clostridioides difficile thrives in inflamed environment, research finds

The inflammation caused by Clostridioides difficile (C. diff) infection gives the pathogen a two-fold advantage: by both creating an inhospitable environment for competing bacteria and providing nutrients that enable C. diff to thrive, according to new research from North Carolina State University published in the journal Nature Communications.

For the study, researchers studied two varieties of C. diff, one that produced the toxins and a genetically modified strain that did not, both in vitro and in a mouse model. In both models, toxin-producing C. diff was associated with increased inflammation and cellular damage, according to the study.

Genetic analysis found that C. diff in an inflamed environment expressed more genes related to carbohydrate and amino acid metabolism. Finally, in vitro experiments demonstrated that C. diff was able to utilize amino acids from collagen for growth.

The study found that C. diff toxins damage the cells that line the gut. These cells contain collagen, the researchers said, which is made up of amino acids and peptides. When collagen is degraded by toxins, C. diff responds by turning on expression of genes that can use these amino acids for growth.

The researchers also noted that an inflamed environment suppressed the numbers of other microbes in the gut. Therefore, the toxins play a dual role: by causing inflammation, C. diff both removes competition for resources and creates more resources for its own growth, the researchers said.

"C. diff thrives when other microbes in the gut are absent, which is why it is more prevalent following antibiotic therapy," said Casey Theriot, PhD, corresponding author of the study and associate professor of infectious disease at North Carolina State University, in a statement. "But when colonizing the gut, C. diff also produces two large toxins, TcdA and TcdB, which cause inflammation. We wanted to know if these inflammation-causing toxins actually give C. diff a survival benefit, whether the pathogen can exploit an inflamed environment in order to thrive."

The study, co-led by Josh Fletcher, PhD, former postdoctoral researcher at North Carolina State University, concluded that the intense inflammation caused by C. diff may contribute to the persistence in the gut environment, prolonging infection.