Precision microbiome reconstitution restores bile acid mediated resistance to Clostridium difficile Journal Article


Authors: Buffie, C. G.; Bucci, V.; Stein, R. R.; McKenney, P. T.; Ling, L. L.; Gobourne, A.; No, D.; Liu, H.; Kinnebrew, M.; Viale, A.; Littmann, E.; van den Brink, M. R. M.; Jenq, R. R.; Taur, Y.; Sander, C.; Cross, J. R.; Toussaint, N. C.; Xavier, J. B.; Pamer, E. G.
Article Title: Precision microbiome reconstitution restores bile acid mediated resistance to Clostridium difficile
Abstract: The gastrointestinal tracts of mammals are colonized by hundreds of microbial species that contribute to health, including colonization resistance against intestinal pathogens(1). Many antibiotics destroy intestinal microbial communities and increase susceptibility to intestinal pathogens(2). Among these, Clostridium difficile, a major cause of antibiotic-induced diarrhoea, greatly increases morbidity and mortality in hospitalized patients(3). Which intestinal bacteria provide resistance to C. difficile infection and their in vivo inhibitory mechanisms remain unclear. Here we correlate loss of specific bacterial taxa with development of infection, by treating mice with different antibiotics that result in distinct microbiota changes and lead to varied susceptibility to C. difficile. Mathematical modelling augmented by analyses of the microbiota of hospitalized patients identifies resistance-associated bacteria common to mice and humans. Using these platforms, we determine that Clostridium scindens, a bile acid 7 alpha-dehydroxylating intestinal bacterium, is associated with resistance to C. difficile infection and, upon administration, enhances resistance to infection in a secondary bile acid dependent fashion. Using a workflow involving mouse models, clinical studies, metagenomic analyses, and mathematical modelling, we identify a probiotic candidate that corrects a clinically relevant microbiome deficiency. These findings have implications for the rational design of targeted antimicrobials as well as microbiome-based diagnostics and therapeutics for individuals at risk of C. difficile infection.
Keywords: metabolism; transplantation; colonization; phylogeny; intestinal microbiota; domination; spore germination; sequencing data; communities; human feces
Journal Title: Nature
Volume: 517
Issue: 7533
ISSN: 0028-0836
Publisher: Nature Publishing Group  
Date Published: 2015-01-08
Start Page: 205
End Page: 208
Language: English
ACCESSION: WOS:000347477600037
DOI: 10.1038/nature13828
PROVIDER: wos
PUBMED: 25337874
PMCID: PMC4354891
Notes: Article -- Source: Wos
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MSK Authors
  1. Eric Pamer
    283 Pamer
  2. Robert R Jenq
    107 Jenq
  3. Agnes Viale
    245 Viale
  4. Vanni Bucci
    8 Bucci
  5. Chris Sander
    210 Sander
  6. Joao Debivar Xavier
    97 Xavier
  7. Justin Robert Cross
    111 Cross
  8. Ying Taur
    147 Taur
  9. Richard Rainer Stein
    3 Stein
  10. Daniel Christopher No
    5 No
  11. Charlie G Buffie
    7 Buffie
  12. Lilan Ling
    44 Ling
  13. Hui   Liu
    8 Liu