title: Changes in Colonic Bile Acid Composition following Fecal Microbiota Transplantation Are Sufficient to Control Clostridium difficile Germination and Growth.
abstract: Fecal microbiota transplantation (FMT) is a highly effective therapy for recurrent Clostridium difficile infection (R-CDI), but its mechanisms remain poorly understood. Emerging evidence suggests that gut bile acids have significant influence on the physiology of C. difficile, and therefore on patient susceptibility to recurrent infection. We analyzed spore germination of 10 clinical C. difficile isolates exposed to combinations of bile acids present in patient feces before and after FMT. Bile acids at concentrations found in patients' feces prior to FMT induced germination of C. difficile, although with variable potency across different strains. However, bile acids at concentrations found in patients after FMT did not induce germination and inhibited vegetative growth of all C. difficile strains. Sequencing of the newly identified germinant receptor in C. difficile, CspC, revealed a possible correspondence of variation in germination responses across isolates with mutations in this receptor. This may be related to interstrain variability in spore germination and vegetative growth in response to bile acids seen in this and other studies. These results support the idea that intra-colonic bile acids play a key mechanistic role in the success of FMT, and suggests that novel therapeutic alternatives for treatment of R-CDI may be developed by targeted manipulation of bile acid composition in the colon.
authors.affiliation: Department of Microbiology and Immunology, University of Minnesota, St. Paul, Minnesota, United States of America.|The BioTechnology Institute, University of Minnesota, St. Paul, Minnesota, United States of America.
authors.forename: Alexa R
authors.initials: AR
authors.lastname: Weingarden
authors.affiliation: Department of Medicinal Chemistry-Institute for Therapeutics Discovery and Development, University of Minnesota, Minneapolis, Minnesota, United States of America.
authors.forename: Peter I
authors.initials: PI
authors.lastname: Dosa
authors.affiliation: The BioTechnology Institute, University of Minnesota, St. Paul, Minnesota, United States of America.
authors.forename: Erin
authors.initials: E
authors.lastname: DeWinter
authors.affiliation: Department of Medicine, University of Minnesota, Minneapolis, Minnesota, United States of America.|Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, Minnesota, United States of America.
authors.forename: Clifford J
authors.initials: CJ
authors.lastname: Steer
authors.affiliation: Department of Medicine, Division of Infectious Diseases, University of Minnesota, Minneapolis, Minnesota, United States of America.|Minneapolis Veterans Affairs (VA) Healthcare System, Division of Infectious Diseases, Minneapolis, Minnesota, United States of America.
authors.forename: Megan K
authors.initials: MK
authors.lastname: Shaughnessy
authors.affiliation: Department of Medicine, Division of Infectious Diseases, University of Minnesota, Minneapolis, Minnesota, United States of America.|Minneapolis Veterans Affairs (VA) Healthcare System, Division of Infectious Diseases, Minneapolis, Minnesota, United States of America.
authors.forename: James R
authors.initials: JR
authors.lastname: Johnson
authors.affiliation: The BioTechnology Institute, University of Minnesota, St. Paul, Minnesota, United States of America.|Department of Medicine, Division of Gastroenterology, University of Minnesota, Minneapolis, Minnesota, United States of America.|Center for Immunology, University of Minnesota, Minneapolis, Minnesota, United States of America.
authors.forename: Alexander
authors.initials: A
authors.lastname: Khoruts
authors.affiliation: The BioTechnology Institute, University of Minnesota, St. Paul, Minnesota, United States of America.|Department of Soil, Water & Climate, University of Minnesota, St. Paul, Minnesota, United States of America.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Sadowsky
mesh_terms: D001647:Bile Acids and Salts / Q000378:metabolism*; D001691:Biological Therapy / Q000379:methods*; D016360:Clostridioides difficile / Q000254:growth & development* / Q000302:isolation & purification / Q000472:pathogenicity; D003106:Colon / Q000378:metabolism* / Q000382:microbiology; D004761:Enterocolitis, Pseudomembranous / Q000382:microbiology / Q000517:prevention & control*; D000069467:Fecal Microbiota Transplantation; D005243:Feces / Q000382:microbiology*; D006801:Humans
chemical_list: D001647:Bile Acids and Salts