Study: Inflamed Environment Is Ideal for C. diff

Inflammation caused by clostridioides difficile (C. diff) not only creates an inhospitable environment for competing bacteria, but it also provides nutrients that allow C. diff to thrive, according to researchers from North Carolina State University.

C. diff causes severe diarrhea, which can have severe or fatal consequences. As part of the bacteria’s growth cycle, it produces 2 toxins that cause inflammation and damage the stomach lining. These toxins give it the 2 advantages, according to the investigators.

“C. diff thrives when other microbes in the gut are absent—which is why it is more prevalent following antibiotic therapy,” said corresponding author Casey Theriot, PhD, associate professor of infectious diseases at NC State, in the press release. “But when colonizing the gut, C. diff also produces 2 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 researchers examined 2 varieties of C. diff—one that produced the toxins and a second, genetically-modified strain that did not. In both models, toxin-producing C. diff was associated with increased inflammation and cellular damage.

Furthermore, a genetic analysis found that C. diff in an inflamed environment expressed more genes related to carbohydrate and amino acid metabolism. In vitro experiments also found that C. diff was able to utilize amino acids from collagen for growth.

“C. diff’s toxins damage the cells that line the gut,” Theriot said in the press release. “These cells contain collagen, 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.”

In addition to these findings, the authors noted that an inflamed environment suppressed the numbers of other microbes in the gut, removing competition for other resources while simultaneously creating even more resources for its own growth.

“I always found it interesting that C. diff causes such intense inflammation,” said researcher Josh Fletcher, a postdoctoral researcher at NC State, in the press release. “Our research shows that this inflammation may contribute to the persistence of C. diff in the gut environment, prolonging infection.”

REFERENCE

Inflamed Environment Is C. diff Paradise [news release]. NC State University; January 19, 2021. https://news.ncsu.edu/2021/01/inflamed-environment-is-c-diff-paradise/. Accessed March 9, 2021.