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

Lawley, Trevor D.; Clare, Simon; Walker, Alan W.; Stares, Mark D.; Connor, Thomas R.; Raisen, Claire; Goulding, David; Rad, Roland; Schreiber, Fernanda; Brandt, Cordelia; Deakin, Laura J.; Pickard, Derek J.; Duncan, Sylvia H.; Flint, Harry J.; Clark, Taane G.; Parkhill, Julian; Dougan, Gordon
October 2012
PLoS Pathogens;Oct2012, Vol. 8 Issue 10, Special section p1
Academic Journal
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.


Related Articles

  • Commentary: Reducing Viability Bias in Analysis of Gut Microbiota in Preterm Infants at Risk of NEC and Sepsis. Agustí, Gemma; Codony, Francesc // Frontiers in Cellular & Infection Microbiology;6/20/2018, Vol. 8, pN.PAG 

    A commentary is presented on the reduction of the viability bias in gut microbiota analysis in preterm infants at risk of sepsis and necrotizing enterocolitis.

  • What Factors Lead to Acquisition of Clostridium difficile?  // Hospital Medicine Alert;Jan2012 Clinical Briefs Supplement, p2 

    The article focuses on the study by V. G. Loo and colleagues which examined the host and pathogen factors associated to Clostridium difficile colonization and infection.

  • Reducing the Incidence of Clostridium Difficile Infections: Can We Do It? Pop-Vicas, Aurora; Butterfield, Kristen; Gardner, Rebekah // Medicine & Health Rhode Island;Sep2010, Vol. 93 Issue 9, p263 

    The article focuses on various challenges in controlling Clostridium difficile infections (CDI) and infection control efforts to reduce the incidence of CDI. It notes that Clostridium difficile (C. difficile) is a pathogen that has become endemic in the U.S. and Europe and has become more...

  • Hyper virulent strain of C diff hits Australia.  // Lamp;2010, Vol. 67 Issue 6, p12 

    The article discusses cases of a hyper virulent strain of Clostridium difficile infection which have been reported in Australia in 2010.

  • Reply to McDonald. Walk, Seth T.; Micic, Dejan; Galecki, Andrzej T.; Rogers, Mary A. M.; Washer, Laraine; Newton, Duane W.; Malani, Preeti N.; Young, Vincent B.; Aronoff, David M. // Clinical Infectious Diseases;Mar2013, Vol. 56 Issue 6, p907 

    A response from the author of the article "Clostridium difficile ribotype does not predict severe infection" in the 2012 issue is presented.

  • Asymptomatic C. difficile colonization prevalent at hospital admission.  // Infectious Disease News;May2014, Vol. 27 Issue 5, p51 

    THe article on the prevalence of colonization with toxigenic Clostridium difficile among asymptomatic individuals who were admitted to the hospital, according to researchers from Washington University School of Medicine.

  • Fecal-Free Toxin Detection Remains the Best Way to Detect Clostridium difficile Infection. Planche, Tim; Wilcox, Mark; Walker, A. Sarah; Rao, Krishna; Young, Vincent B.; Aronoff, David M. // Clinical Infectious Diseases;10/1/2015, Vol. 61 Issue 7, p1210 

    A response from the authors of the article "Fecal free toxin detection remains the best way to detect Clostridium difficile infection" is presented.

  • Rapidly Progressive Necrotizing Fascitis and Gangrene Due to Clostridium difficile: Case Report. Bhargava, Abha; Sen, Purnendu; Swaminathan, Anangur; Ogbulu, Cora; Chechko, Susan; Stone, Frederick // Clinical Infectious Diseases;6/1/2000, Vol. 30 Issue 6, p954 

    Describes a case of rapidly progressive necrotizing fascitis and gas gangrene due to Clostridium difficile. Treatment received by the patient; Diseases associated with C. difficile.

  • Dijareja izazvana Clostridium difficile kod bolesnika sa postoperativnim suphepatičnim apscesom. Stojanović, Predrag; Kocić, Branislava // Vojnosanitetski Pregled: Military Medical & Pharmaceutical Journ;Mar2008, Vol. 65 Issue 3, p249 

    Background. Toxigenic strains of Clostridium difficile in the majority of cases cause disease of the intestinal tract of hospitalized patients. For a long time, Clostridium difficile was considered to produce both types of toxins (A+/B+ strain), however, the investigations conducted in the last...


Read the Article

Courtesy of

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics