1795. Quantitative Responses of Taxonomic Composition and Resistance Gene Abundance in the Gut Microbiota to Fecal Microbiota Transplantation
Session: Oral Abstract Session: Resistance is Futile
Saturday, October 29, 2016: 11:09 AM
Room: 288-290
Project Title: Quantitative Responses of Taxonomic Composition and Resistance Gene Abundance in the Gut Microbiota to Fecal Microbiota Transplantation Authors: Amy Langdon1, Christopher Bulow1, Kim Reske2, Sherry Sun1, Tiffany Hink2, Courtney Jones3, Carey-Ann D. Burnham1,2, Erik R. Dubberke1,2, Gautam Dantas1 Affiliations: 1Washington University School of Medicine, 2Barnes Jewish Hospital, 3Rebiotix, Inc., Minneapolis, MN. Background: Clostridium difficile is the most common cause of infectious antibiotic associated diarrhea. It frequently recurs, and fecal microbiota transplantation (FMTs) is emerging as a therapeutic option. The objective of this study was to characterize the effects of FMT on relative taxonomic abundance and antibiotic resistance (AR) genes in 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) from one of four healthy donors as part of a phase 2 trial (Rebiotix, Inc.). Samples were collected prior to FMT and at intervals up to 6 months post FMT and analyzed in three ways: 1) 16S sequencing for taxonomic identification, 2) whole genome shotgun sequencing for gene quantitation, and 3) functional metagenomic selections to identify novel AR genes. Results: Successful FMTs showed a clear taxonomic convergence of the patient microbiome to the donor microbiome (Figure 1). Functional selections identified AR genes conferring resistance to 16 out of 18 clinically relevant antibiotics. For AR genes originating from the patient, preliminary analysis shows a downward trend in AR gene abundance after FMT (Figure 2). Conclusion: Successful FMTs may be able reduce the prevalence of AR genes in the recipient gut microbiome. This could potentially reduce the recipientÕs risk of later AR infections and transmission of AR genes to pathogens and to other people. Figure 1. Successful FMTs showed convergence of baseline samples (blue circle) with donor samples (red circle) over time (N=7). Approved%20website%20pictures/16S_progressuib.jpg Figure 2. AR genes were quantified by annotation of shotgun sequencing data before and after successful FMTs in patients with no post-FMT antibiotic use (N=5). ../Downloads/Approved%20website%20pictures/Argenect_biggerlabels.jpg                
Amy Langdon, BA1, Christopher Bulow, BA1, Kimberly Reske, MPH2, Xiaoqing Sun, MS1, Tiffany Hink, BS3, Courtney Jones, BS4, Carey-Ann D. Burnham, PhD5, Erik R. Dubberke, MD, MSPH, FIDSA, FSHEA6 and Gautam Dantas, PhD1, (1)Washington University in St. Louis, St. Louis, MO, (2)Infectious Diseases, Washington University School of Medicine, St. Louis, MO, (3)Infectious Diseases, Washington University School of Medicine, St Louis, MO, (4)Rebiotix Inc., Roseville, MN, (5)Pathology & Immunology, Washington University, St. Louis, MO, (6)Washington University School of Medicine, St. Louis, MO

Disclosures:

A. Langdon, None

C. Bulow, None

K. Reske, None

X. Sun, None

T. Hink, None

C. Jones, Rebiotix Inc.: Employee , Salary

C. A. D. Burnham, None

E. R. Dubberke, Rebiotix Inc.: Investigator and Scientific Advisor , Consulting fee and Research support
Merck: Consultant and Investigator , Consulting fee and Research support
Sanofi Pasteur: Consultant and Grant Investigator , Consulting fee and Grant recipient
Summitt: Consultant , Consulting fee

G. Dantas, None

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