Ursodeoxycholic Acid Inhibits Clostridium difficile Spore Germination and Vegetative Growth, and Prevents the Recurrence of Ileal Pouchitis Associated With the Infection.
To test whether ursodeoxycholic acid (UDCA) is inhibitory to Clostridium difficile and can be used in the treatment of C. difficile-associated ileal pouchitis.



The restoration of secondary bile metabolism may be the key mechanism for fecal microbiota transplantation (FMT) in treating recurrent C. difficile infections (RCDI). Therefore, it is possible that exogenous administration of inhibitory bile acids may be used directly as nonantibiotic therapeutics for this indication. The need for such a treatment alternative is especially significant in patients with refractory C. difficile-associated pouchitis, where the efficacy of FMT may be limited.



We measured the ability of UDCA to suppress the germination and the vegetative growth of 11 clinical isolate strains of C. difficile from patients treated with FMT for RCDI. In addition, we used oral UDCA to treat a patient with RCDI pouchitis that proved refractory to multiple antibiotic treatments and FMT.



UDCA was found to be inhibitory to the germination and the vegetative growth of all C. difficile strains tested. Fecal concentrations of UDCA from the patient with RCDI pouchitis exceeded levels necessary to inhibit the germination and the growth of C. difficile in vitro. The patient has remained infection free for over 10 months after the initiation of UDCA.



UDCA can be considered as a therapeutic option in patients with C. difficile-associated pouchitis. Further studies need to be conducted to define the optimal dose and duration of such a treatment. In addition, bile acid derivatives inhibitory to C. difficile that are able to achieve high intracolonic concentrations may be developed as therapeutics for RCDI colitis.
Departments of *Microbiology and The BioTechnology Institute †Food Science and Nutrition ‡Medicine, Division of Gastroenterology, Center for Immunology, BioTechnology Institute §Medicinal Chemistry, Institute for Therapeutics Discovery and Development ∥Medicine and Genetics, Cell Biology, and Development ¶Medicine, Division of Infectious Diseases **Soil, Water & Climate, and The BioTechnology Institute, University of Minnesota #Minneapolis Veterans Affairs Healthcare System, Minneapolis, MN.
Alexa R
AR
Weingarden
Chi
C
Chen
Ningning
N
Zhang
Carolyn T
CT
Graiziger
Peter I
PI
Dosa
Clifford J
CJ
Steer
Megan K
MK
Shaughnessy
James R
JR
Johnson
Michael J
MJ
Sadowsky
Alexander
A
Khoruts
D001647:Bile Acids and Salts / Q000378:metabolism; D016360:Clostridioides difficile / Q000302:isolation & purification*; D003015:Clostridium Infections / Q000188:drug therapy* / Q000473:pathology; D000069467:Fecal Microbiota Transplantation; D005243:Feces / Q000382:microbiology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008875:Middle Aged; D019449:Pouchitis / Q000188:drug therapy* / Q000382:microbiology; D012008:Recurrence; D016896:Treatment Outcome; D014580:Ursodeoxycholic Acid / Q000008:administration & dosage* / Q000494:pharmacology
D001647:Bile Acids and Salts; D014580:Ursodeoxycholic Acid