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.
Original language | English |
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Article number | e1002995 |
Number of pages | 14 |
Journal | PLoS Pathogens |
Volume | 8 |
Issue number | 10 |
DOIs | |
Publication status | Published - 25 Oct 2012 |
Keywords
- transplantation
- susceptibility
- epidemic
- strain
- infection
- antibiotic perturbation
- diarrhea
- transmission
- inflammation
- enterica serovar typhimurium
- vancomycin
- animals
- clostridium difficile
- drug resistance
- bacterial
- enterocolitis
- pseudomembranous
- feces
- female
- intestines
- mice
- mice, inbred C3H,
- microbial consortia
- microbial interactions
- molecular sequence data
- probiotics
- recurrence