Humanized microbiota mice as a model of recurrent Clostridium difficile disease.
BACKGROUND
Clostridium difficile disease is the leading antibiotic-associated cause of diarrhea and nosocomial acquired infection in the western world. The per annum burden in the USA alone amounts to 250,000 cases with 14,000 ascribed deaths and medical costs in excess of a billion dollars. Novel models for the study of C. difficile infection are therefore pertinent.


RESULTS
Germ free C57BL/6 mice gavaged with a healthy human fecal microbiota maintained a stable "humanized" microbiota over multiple generations when housed under specific pathogen-free (SPF) conditions. As with mice containing a conventional microbiota, treatment with a five-antibiotic cocktail followed by a single dose of clindamycin renders the animals susceptible to C. difficile infection (CDI). Interestingly, after recovery from the initial CDI infection, a single intraperitoneal injection of clindamycin is sufficient to induce CDI relapse. Relapse of CDI can be induced up to 35 days postinfection after recovery from the initial infection, and multiple episodes of relapse can be induced.


CONCLUSIONS
This model enables the study of recurrent C. difficile disease in a host containing a human-derived microbiota. Probiotic treatments using human-derived microbes, either prophylactic or curative, can be tested within the model. The identification and testing of human-derived microbial communities within a humanized microbiota mouse model may enable a higher rate of successful transfer of bacteria-based treatments from the lab to human patients due to the microbes involved initiating from, and being adapted to, the human GI tract.
Baylor College of Medicine, Department of Molecular Virology and Microbiology, Alkek Center for Metagenomics and Microbiome Research, Houston, TX, USA. James.collins@bcm.edu.
James
J
Collins
Baylor College of Medicine, Department of Molecular Virology and Microbiology, Alkek Center for Metagenomics and Microbiome Research, Houston, TX, USA. Jennifer.Auchtung@bcm.edu.
Jennifer M
JM
Auchtung
Baylor College of Medicine, Department of Molecular Virology and Microbiology, Alkek Center for Metagenomics and Microbiome Research, Houston, TX, USA. laura.schaefer2@bcm.edu.
Laura
L
Schaefer
Department of Microbiology and Immunology, University of Michigan, Ann Arbor, MI, USA. kateaton@umich.edu.
Kathryn A
KA
Eaton
Baylor College of Medicine, Department of Molecular Virology and Microbiology, Alkek Center for Metagenomics and Microbiome Research, Houston, TX, USA. Robert.Britton@bcm.edu.
Robert A
RA
Britton
D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000494:pharmacology; D001419:Bacteria / Q000145:classification / Q000235:genetics; D044822:Biodiversity; D016360:Clostridioides difficile; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D004761:Enterocolitis, Pseudomembranous / Q000188:drug therapy / Q000382:microbiology*; D005243:Feces / Q000382:microbiology; D006801:Humans; D051379:Mice; D064307:Microbiota / Q000187:drug effects; D012008:Recurrence
D000900:Anti-Bacterial Agents