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Targeted restoration of the intestinal microbiota with a simple, defined bacteriotherapy resolves relapsing clostridium difficile disease in mice

Lawley, Trevor D., Clare, Simon, Walker, Alan W., Stares, Mark D., Connor, Thomas Richard, Raisen, Claire, Goulding, David, Rad, Roland, Schreiber, Fernanda, Brandt, Cordelia, Deakin, Laura J., Pickard, Derek J., Duncan, Sylvia H., Flint, Harry J., Clark, Taane G., Parkhill, Julian and Dougan, Gordon 2012. Targeted restoration of the intestinal microbiota with a simple, defined bacteriotherapy resolves relapsing clostridium difficile disease in mice. PLoS Pathogens 8 (10) , e1002995. 10.1371/journal.ppat.1002995

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Abstract

Relapsing C. difficile disease in humans is linked to a pathological imbalance within the intestinal microbiota, termed dysbiosis, which remains poorly understood. We show that mice infected with epidemic C. difficile (genotype 027/BI) develop highly contagious, chronic intestinal disease and persistent dysbiosis characterized by a distinct, simplified microbiota containing opportunistic pathogens and altered metabolite production. Chronic C. difficile 027/BI infection was refractory to vancomycin treatment leading to relapsing disease. In contrast, treatment of C. difficile 027/BI infected mice with feces from healthy mice rapidly restored a diverse, healthy microbiota and resolved C. difficile disease and contagiousness. We used this model to identify a simple mixture of six phylogenetically diverse intestinal bacteria, including novel species, which can re-establish a health-associated microbiota and clear C. difficile 027/BI infection from mice. Thus, targeting a dysbiotic microbiota with a defined mixture of phylogenetically diverse bacteria can trigger major shifts in the microbial community structure that displaces C. difficile and, as a result, resolves disease and contagiousness. Further, we demonstrate a rational approach to harness the therapeutic potential of health-associated microbial communities to treat C. difficile disease and potentially other forms of intestinal dysbiosis.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Systems Immunity Research Institute (SIURI)
Subjects: Q Science > QH Natural history > QH301 Biology
Q Science > QR Microbiology > QR180 Immunology
Q Science > QR Microbiology > QR355 Virology
Publisher: Public Library of Science
ISSN: 1553-7374
Date of First Compliant Deposit: 30 March 2016
Last Modified: 04 Jun 2017 04:37
URI: http://orca-mwe.cf.ac.uk/id/eprint/41534

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