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Open Access Highly Accessed Methodology

Stool substitute transplant therapy for the eradication of Clostridium difficile infection: ‘RePOOPulating’ the gut

Elaine O Petrof1*, Gregory B Gloor2, Stephen J Vanner1, Scott J Weese3, David Carter4, Michelle C Daigneault5, Eric M Brown5, Kathleen Schroeter5 and Emma Allen-Vercoe5

  • * Corresponding author: Elaine O Petrof eop@queensu.ca

  • † Equal contributors

Author Affiliations

1 Department of Medicine, GIDRU Wing, Kingston General Hospital, Queen’s University, 76 Stuart Street, Kingston, ON, K7L 2V7, Canada

2 Department of Biochemistry, University of Western Ontario, 1151 Richmond Street, London, ON, N6A 3K7, Canada

3 Department of Pathobiology, University of Guelph, Guelph, 50 Stone Road East, ON, N1G 2W1, Canada

4 London Regional Genomics Centre, Robarts Research Institute, 100 Perth Drive, London, ON, N6A 5K8, Canada

5 Department of Molecular and Cellular Biology, University of Guelph, 50 Stone Road East, Guelph, ON, N1G 2W1, Canada

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Microbiome 2013, 1:3  doi:10.1186/2049-2618-1-3

Published: 9 January 2013

Abstract

Background

Fecal bacteriotherapy (‘stool transplant’) can be effective in treating recurrent Clostridium difficile infection, but concerns of donor infection transmission and patient acceptance limit its use. Here we describe the use of a stool substitute preparation, made from purified intestinal bacterial cultures derived from a single healthy donor, to treat recurrent C. difficile infection that had failed repeated standard antibiotics. Thirty-three isolates were recovered from a healthy donor stool sample. Two patients who had failed at least three courses of metronidazole or vancomycin underwent colonoscopy and the mixture was infused throughout the right and mid colon. Pre-treatment and post-treatment stool samples were analyzed by 16 S rRNA gene sequencing using the Ion Torrent platform.

Results

Both patients were infected with the hyper virulent C. difficile strain, ribotype 078. Following stool substitute treatment, each patient reverted to their normal bowel pattern within 2 to 3 days and remained symptom-free at 6 months. The analysis demonstrated that rRNA sequences found in the stool substitute were rare in the pre-treatment stool samples but constituted over 25% of the sequences up to 6 months after treatment.

Conclusion

This proof-of-principle study demonstrates that a stool substitute mixture comprising a multi-species community of bacteria is capable of curing antibiotic-resistant C. difficile colitis. This benefit correlates with major changes in stool microbial profile and these changes reflect isolates from the synthetic mixture.

Trial registration

Clinical trial registration number: CinicalTrials.gov NCT01372943

Keywords:
Clostridium difficile; Fecal bacteriotherapy; Probiotics; Gut microbiome