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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Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/e29efcffca5d4832924a324b0e3c1a00
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spelling	oai:doaj.org-article:e29efcffca5d4832924a324b0e3c1a002021-11-18T06:06:25ZTargeted restoration of the intestinal microbiota with a simple, defined bacteriotherapy resolves relapsing Clostridium difficile disease in mice.1553-73661553-737410.1371/journal.ppat.1002995https://doaj.org/article/e29efcffca5d4832924a324b0e3c1a002012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23133377/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Relapsing 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.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 DouganPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 8, Iss 10, p e1002995 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 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.
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
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
title	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_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_sort	targeted restoration of the intestinal microbiota with a simple, defined bacteriotherapy resolves relapsing clostridium difficile disease in mice.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/e29efcffca5d4832924a324b0e3c1a00
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Targeted restoration of the intestinal microbiota with a simple, defined bacteriotherapy resolves relapsing Clostridium difficile disease in mice.

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