is a harmful bacterium that can cause severe, recurrent and sometimes fatal infections in the gut. Although the bacteria are commonly found throughout our environment,
infections primarily occur in patients who are taking, or who have recently finished taking, antibiotics.
"We know that antibiotics
are major risk factors for C. diff
infection because they alter the gut microbiota, or composition of bacteria in the gut, by eliminating the bacteria that are normally there," says Casey Theriot, assistant professor of infectious disease at NC State and corresponding author of a paper describing the research. "Our latest work suggests that the microbiota may provide natural resistance to C. diff
colonization by competing with C. diff
for nutrients in that environment; specifically, for an amino acid called proline."
Theriot and postdoctoral fellow Joshua Fletcher introduced C. diff
to antibiotic-treated mice and monitored their gut environment at four intervals: 0, 12, 24, and 30 hours after introduction. They conducted metabolomic and RNA sequencing analysis of the gut contents and the C. diff
at these time points to find out which nutrients the bacteria were "eating." Metabolomics allowed the team to trace the abundance of the nutrients in the gut, and RNA analysis indicated which genes in the C. diff
were active in metabolizing nutrients.
The researchers found that the amount of proline in the gut decreased as the population of C. diff
increased. Additionally, the amount of a proline byproduct called 5-aminovalerate also increased, indicating that C. diff
was metabolizing the proline. The RNA analysis further confirmed C. diff'
s use of proline, as genes related to proline metabolism in C. diff
increased during the early stages of colonization, when proline was abundant.
"We've been able to show that in the absence of competition C. diff
is metabolizing proline and other amino acids in the mouse model, using it as fuel to survive and thrive," Theriot says. "Hopefully this information could lead to the development of better probiotics, or 'good' bacteria that can outcompete C. diff
for nutrients in the gut. The ultimate goal is to control these bacteria in ways that don't rely solely on antibiotics."