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 ORCID: https://orcid.org/0000-0003-2394-6504, 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:	15 May 2023 06:56
URI:	https://orca.cardiff.ac.uk/id/eprint/41534

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