1197 - Inhibitory Effect of Ursodeoxycholic Acid on Clostridioides difficile Growth

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Presenting Author(s)

FA

Faris S. Alnezary

Postdoctoral Fellow
University of Houston College of Pharmacy
Houston, Texas
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.

Co-Author(s)

M Jahangir Alam

Assistant Research Professor
Department of Pharmacy Practice and Translational Research, University of Houston College of Pharmacy, Houston, Texas, USA
Houston, Texas
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
MA

Masaad Almutairi

A novel method to assess virulence of Clostridioides difficile: Focus on C. difficile ribotype 106
University of Houston
Pearland, Texas
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
SF

Saad Fallatah

Post Doctoral Fellow
University of Houston
Houston, Texas
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
Khurshida Begum

Research scientist
Department of Pharmacy Practice and Translational Research, University of Houston College of Pharmacy, Houston, Texas, USA
Houston, Texas
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
Anne J. Gonzales-Luna

Assistant Professor
Department of Pharmacy Practice and Translational Research, University of Houston College of Pharmacy
Houston, TX
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
Kevin W. Garey

Professor and Chair
University of Houston
Houston, TX
Disclosure: Merck & Co. (Grant/Research Support, Scientific Research Study Investigator)

Background: Ursodeoxycholic acid (UDCA), a secondary bile acid, inhibits germination and growth of Clostridioides difficile in vitro, but the results from in vivo experiments have been conflicting. We evaluated the effects of UDCA on C. difficile in vitro and in a wax moth, Galleria mellonella model.

Methods: The in vitro growth and germination effects of UDCA on C. difficile were assessed with increased concentration of UDCA (0.001, 0.01, 0.05, and 0.1%). To assess treatment effects of UDCA, C. difficile spores (approximately 1x10^6-8 colony forming units (CFU)) were force fed to G. mellonella larvae treated with UDCA (50 mg/kg/day) 24 hours prior to C. difficile inoculation. Forty G. mellonella larvae were used for each experiment, which was repeated with two distinct strains (R20291 and CD196). Larvae were housed at 37°C and monitored for the next five days for mortality.

Results: In vitro experiment demonstrated inhibition of C. difficile growth at 0.1% concentration (P < 0.001 vs control). Larvae treated with UDCA had a numerically higher survival rate (60% / 24/40) compared to controls (40% / 16/40) but the results were not statistically significant (p=0.14). Identical rates of survival were observed in the control arms for both strains (40%) and similar in the treatment arms (R20291: 70%; CD 196: 50%).

Conclusion: Overall, UDCA shows inhibitory effect of growth and germination of C. difficile in vitro. However, in our G. mellonella model, a single dose of UDCA given prior to infection did not prevent CDI. Further dose dependent, and multiday studies investigating the role of UDCA in CDI is needed to better understand this in vitro / in vivo paradox.