Targeted Restoration of the Intestinal Microbiota with a Simple, Defined Bacteriotherapy Resolves Relapsing Clostridium difficile Disease in Mice

被引：403

作者：

Lawley, Trevor D. ^{[1
]}

Clare, Simon ^{[1
]}

Walker, Alan W. ^{[1
]}

Stares, Mark D. ^{[1
]}

Connor, Thomas R. ^{[1
]}

Raisen, Claire ^{[1
]}

Goulding, David ^{[1
]}

Rad, Roland ^{[1
]}

Schreiber, Fernanda ^{[1
]}

Brandt, Cordelia ^{[1
]}

Deakin, Laura J. ^{[1
]}

Pickard, Derek J. ^{[1
]}

Duncan, Sylvia H. ^{[2
]}

Flint, Harry J. ^{[2
]}

Clark, Taane G. ^{[3
]}

Parkhill, Julian ^{[1
]}

Dougan, Gordon ^{[1
]}

机构：

[1] Wellcome Trust Sanger Inst, Hinxton, England

[2] Rowett Inst Nutr & Hlth, Aberdeen, Scotland

[3] London Sch Hyg & Trop Med, London WC1, England

来源：

PLOS PATHOGENS | 2012年 / 8卷 / 10期

基金：

英国惠康基金; 英国医学研究理事会;

关键词：

ENTERICA SEROVAR TYPHIMURIUM; ANTIBIOTIC PERTURBATION; INFECTION; DIARRHEA; TRANSMISSION; EPIDEMIC; STRAIN; SUSCEPTIBILITY; TRANSPLANTATION; INFLAMMATION;

D O I：

10.1371/journal.ppat.1002995

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

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.

引用

页数：14

共 70 条

[11] Profound Alterations of Intestinal Microbiota following a Single Dose of Clindamycin Results in Sustained Susceptibility to Clostridium difficile-Induced Colitis [J].