Targeted restoration of the intestinal microbiota with a simple, defined bacteriotherapy resolves relapsing Clostridium difficile disease in mice.
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 persis...
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| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS Pathogens |
| Online Access: | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1002995&type=printable |
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| _version_ | 1850224648212447232 |
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| author | Trevor D Lawley Simon Clare Alan W Walker Mark D Stares Thomas R Connor Claire Raisen David Goulding Roland Rad Fernanda Schreiber Cordelia Brandt Laura J Deakin Derek J Pickard Sylvia H Duncan Harry J Flint Taane G Clark Julian Parkhill Gordon Dougan |
| author_facet | Trevor D Lawley Simon Clare Alan W Walker Mark D Stares Thomas R Connor Claire Raisen David Goulding Roland Rad Fernanda Schreiber Cordelia Brandt Laura J Deakin Derek J Pickard Sylvia H Duncan Harry J Flint Taane G Clark Julian Parkhill Gordon Dougan |
| author_sort | Trevor D Lawley |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-e29efcffca5d4832924a324b0e3c1a00 |
| institution | OA Journals |
| issn | 1553-7366 1553-7374 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj-art-e29efcffca5d4832924a324b0e3c1a002025-08-20T02:05:34ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742012-01-01810e100299510.1371/journal.ppat.1002995Targeted restoration of the intestinal microbiota with a simple, defined bacteriotherapy resolves relapsing Clostridium difficile disease in mice.Trevor D LawleySimon ClareAlan W WalkerMark D StaresThomas R ConnorClaire RaisenDavid GouldingRoland RadFernanda SchreiberCordelia BrandtLaura J DeakinDerek J PickardSylvia H DuncanHarry J FlintTaane G ClarkJulian ParkhillGordon DouganRelapsing 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.https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1002995&type=printable |
| spellingShingle | Trevor D Lawley Simon Clare Alan W Walker Mark D Stares Thomas R Connor Claire Raisen David Goulding Roland Rad Fernanda Schreiber Cordelia Brandt Laura J Deakin Derek J Pickard Sylvia H Duncan Harry J Flint Taane G Clark Julian Parkhill Gordon Dougan Targeted restoration of the intestinal microbiota with a simple, defined bacteriotherapy resolves relapsing Clostridium difficile disease in mice. PLoS Pathogens |
| title | Targeted restoration of the intestinal microbiota with a simple, defined bacteriotherapy resolves relapsing Clostridium difficile disease in mice. |
| title_full | Targeted restoration of the intestinal microbiota with a simple, defined bacteriotherapy resolves relapsing Clostridium difficile disease in mice. |
| title_fullStr | Targeted restoration of the intestinal microbiota with a simple, defined bacteriotherapy resolves relapsing Clostridium difficile disease in mice. |
| title_full_unstemmed | Targeted restoration of the intestinal microbiota with a simple, defined bacteriotherapy resolves relapsing Clostridium difficile disease in mice. |
| title_short | Targeted restoration of the intestinal microbiota with a simple, defined bacteriotherapy resolves relapsing Clostridium difficile disease in mice. |
| title_sort | targeted restoration of the intestinal microbiota with a simple defined bacteriotherapy resolves relapsing clostridium difficile disease in mice |
| url | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1002995&type=printable |
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