Project Title: Alteration of the microbial community of the gut in response to fecal microbiota transplantation in subjects with Clostridium difficile infection
Authors: Amy Langdon, Kim Reske, Sherry Sun, Tiffany Hink, Courtney Jones, Carey-Ann D. Burnham, Erik R. Dubberke, Gautam Dantas
Affiliations: Washington University School of Medicine, Barnes Jewish Hospital. Rebiotix, Inc, Minneapolis, MN
Background: Clostridium difficile is the most common cause of infectious antibiotic associated diarrhea. It is often refractory to antimicrobial therapy, and fecal microbiota transplantation (FMTs) is emerging as a therapeutic option. The objective of this study was to characterize the direct effects of FMT on the gut microbiota.
Methods: Fecal specimens were obtained from a cohort of 29 subjects with recurrent C. difficile infection who received either one FMT (N=16) or two FMTs (N=13) as part of a phase 2 trial (Rebiotix). The transplants were prepared from a total of four healthy donors. Fecal specimens were collected from the subject prior to FMT and at intervals up to 6 months post FMT. 16S rRNA gene sequencing and whole-genome shotgun sequencing were used to assess microbial community composition and prevalence of metabolic pathways to quantitatively evaluate the impact of FMT on the gut microbial community.
Results: Initially, the microbial community of subjects with C. difficile infection was distinct from the composition of the healthy donors and was predominated by Proteobacteria. The difference between the patients and the donor (as measure by weighted Unifrac distance) decreased precipitously within the first week (dependent Wilcoxon signed rank test; N=12; p<.0001), and continued to evolve to resemble the donor configuration over the subsequent six months (Figure 1). An increase in that distance was associated with treatment failure (asterisks).
Conclusion: After FMT, the gut microbial community of the recipient evolved in the six months after FMT to resemble that of the donor.
X. Sun, None
T. Hink, None
C. Jones, Rebiotix: Employee , Salary
C. A. D. Burnham, None
E. R. Dubberke, rebiotix: Consultant and Investigator , Consulting fee and Research support
sanofi-pasteur: Grant Investigator , Research grant
pfizer: Consultant , Consulting fee
Merck: Consultant and Investigator , Consulting fee and Research support
G. Dantas, None