Lawley, Trevor D; Clare, Simon; Walker, Alan W; Stares, Mark D; Connor, Thomas R; Raisen, Claire; Goulding, David; Rad, Roland; Schreiber, Fernanda; Brandt, Cordelia; +7 more... Deakin, Laura J; Pickard, Derek J; Duncan, Sylvia H; Flint, Harry J; Clark, Taane G; Parkhill, Julian; 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-. ISSN 1553-7366 DOI: https://doi.org/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 |
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Faculty and Department | Faculty of Infectious and Tropical Diseases > Department of Infection Biology |
Research Centre | Antimicrobial Resistance Centre (AMR) |
PubMed ID | 23133377 |
ISI | 310530300043 |
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