Changes in Colonic Bile Acid Composition following Fecal Microbiota Transplantation Are Sufficient to Control Clostridium difficile Germination and Growth

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 patie...

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Bibliographic Details
Published in:PloS one 2016-01, Vol.11 (1), p.e0147210-e0147210
Main Authors: Weingarden, Alexa R, Dosa, Peter I, DeWinter, Erin, Steer, Clifford J, Shaughnessy, Megan K, Johnson, James R, Khoruts, Alexander, Sadowsky, Michael J
Format: Article
Language:English
Subjects:
Acids
Analysis
Antibiotics
Bile
Bile acids
Bile Acids and Salts - metabolism
Biological Therapy - methods
Biology and Life Sciences
Biotechnology
Chemical properties
Clostridium difficile
Clostridium difficile - growth & development
Clostridium difficile - isolation & purification
Clostridium difficile - pathogenicity
Colon
Colon - metabolism
Colon - microbiology
Deoxycholic acid
Enterocolitis, Pseudomembranous - microbiology
Enterocolitis, Pseudomembranous - prevention & control
Fecal Microbiota Transplantation
Fecal microflora
Feces
Feces - microbiology
Germination
Growth
Health aspects
Humans
Immunology
Infections
Infectious diseases
Medicine
Medicine and Health Sciences
Microbiota
Microbiota (Symbiotic organisms)
Mutation
Nosocomial infections
Patients
Physiological aspects
Recurrent infection
Research and Analysis Methods
Spore germination
Transplantation
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Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0147210