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 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. © 2012 lawley et al.