A commonly used drug made from secondary bile acids can affect the life cycle of Clostridioides difficile.
A commonly used drug made from secondary bile acids can affect the life cycle of Clostridioides difficile (C. diff) in vitro and reduce the inflammatory response to C.diff in mice, according to researchers at North Carolina State University (NC State).
The findings add understanding to how this drug may be used in future treatment of C.diff infections in humans. Ursodiol, ursodeoxycholate (UDCA) is a secondary bile acid made by bacteria in the gut and is also FDA-approved to treat inflammatory liver diseases. It is currently in phase 4 clinical trials for use in treatment of C.diff infections.
“If UDCA proves effective against C. diff infection, it would give us an alternative to antibiotic treatments that further disrupt the gut microbiome and can lead to relapse, or to fecal transplants that may have unknown side effects,” said corresponding study author Casey Theriot, assistant professor of population health and pathobiology at NC State, in a press release.
Theriot and a team of researchers from NC State, Pennsylvania State University, and the University of North Carolina at Chapel Hill looked at UDCA treatment of C.diff in vitro and as a pre-treatment in a mouse model of the disease.
C.diff exists in the environment as a dormant spore, and in humans, the spores colonize the large intestine by germinating, becoming bacteria that produce damaging toxins. The research team had an objective to see whether UDCA would have the same effect in a mouse model.
In vitro, treatment with UDCA significantly decreased C.diff spore germination, growth, and toxin activity. In the mouse model, pre-treatment with UDCA had some effect on bacterial growth, but the main effect of treatment was to suppress the inflammatory response of the immune system to bacterial growth and toxin, according to the press release.
“Mitigating the immune response means that pre-treatment with UDCA could significantly reduce tissue damage due to C. diff infection,” Theriot said in a press release. “This work is the first to explore how UDCA works in vivo against C. diff infection, and demonstrates that the drug may be a viable pre-treatment to help patients avoid damaging effects of a C. diff infection. Our next steps will be to look at dosages and timing, in order to determine how to use it most effectively.”
Drug used to treat liver disease also affects C. diff life cycle, reduces inflammation in mice. NC State University. https://news.ncsu.edu/2020/03/theriot-ursodiol/. Published March 30, 2020. Accessed March 10, 2021.