2012
DOI: 10.1371/journal.ppat.1002995
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Targeted Restoration of the Intestinal Microbiota with a Simple, Defined Bacteriotherapy Resolves Relapsing Clostridium difficile Disease in Mice

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 le… Show more

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Cited by 500 publications
(501 citation statements)
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References 70 publications
(105 reference statements)
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“…In mice, Bacteroides was found to be one of the genera involved in the recovery of disease after bacteriotherapy using a mix of bacteria (Lawley et al, 2012). These results in mice suggest that not a complete microbiota is needed, which may be promising for future therapeutic developments.…”
Section: Discussionmentioning
confidence: 86%
“…In mice, Bacteroides was found to be one of the genera involved in the recovery of disease after bacteriotherapy using a mix of bacteria (Lawley et al, 2012). These results in mice suggest that not a complete microbiota is needed, which may be promising for future therapeutic developments.…”
Section: Discussionmentioning
confidence: 86%
“…26 In both situations manipulation of the microbiome has proven to be a promising method for treating the disease. [14][15][16] In particular, the use of fecal transplant has shown significant efficacy for C.diff infections which have been resistant to several rounds of antibiotic treatment. 39 In a similar mechanism, mice treated with antibiotics recover significantly faster and with greater microbial diversity when co-housed with a normal control mouse, due to natural coprophagic activity.…”
Section: Discussionmentioning
confidence: 99%
“…13 Meta analysis of trials utilizing probiotics in the context of disease states has shown some efficacy. [14][15][16] However, the impact on a microbiome devastated by antibiotic treatment has not been well characterized. This study sought to determine the impacts of a mixed probiotic on the diversity of cecal and large intestinal contents of mice when taken during antibiotic treatment or throughout the recovery phase following antibiotic treatment.…”
Section: Introductionmentioning
confidence: 99%
“…Likewise, Lawley et al used mice infected with the epidemic C. difficile 027/B1, showing that it outcompeted health-associated intestinal bacteria to perpetuate intestinal dysbiosis after clindamycin treatment. This murine model was then employed to rationally identify a simple mixture of six phylogenetically diverse bacteria that triggered the expansion of health-associated bacteria when administered as a mixture rather than as individual species, suggesting that both species composition and diversity are important factors in the design of bacteriotherapy [98]. These examples provide further proof of concept that targeted bacteriotherapy can cause robust shifts in microbial community structure, leading to disease resolution, and further support the rational approach of harnessing healthy microbial communities to treat diseases resulting from intestinal dysbiosis.…”
Section: Microbial Ecosystem Therapeuticsmentioning
confidence: 99%