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71
Alterations in the Gut Microbiome in Recurrent Clostridium difficile Infection

Session: Oral Abstract Session: Bacterial Pathogenesis
Thursday, October 9, 2014: 8:30 AM
Room: The Pennsylvania Convention Center: 109-AB
Background: Clostridium difficile infection (CDI) causes 3 million cases of diarrhea and colitis in the US annually. Although standard antibiotic is effective in suppressing C. difficile, it does not prevent relapse. Indeed, 15 to 30% of patients experience recurrence within 3 months following antibiotic treatment. Recovery of the gut microbiota has been proposed as an important key factor in preventing recurrent C. difficile. However, the stability and responsiveness of gut microbiota following C. difficile treatment and their relationship to recurrence is poorly understood. We have previously showed that Lachnospiraceae, Ruminococcaceae and butyrogenic bacteria are depleted in patients with CDI. We hypothesize that persistent depletion of these organisms is associated with recurrent CDI.

Methods: Culture-independent high-density Roche/454 pyrosequencing was used to characterize distal gut microbiota of 30 adults following CDI sampled longitudinally for up to 1 year, and compared to fecal microbiota from 14 healthy controls.

Results: We analyzed ~2 million partial V1-V3 16S rRNA sequences from ~500 longitudinal fecal samples, identifying a total of 5,904 bacterial phylotypes. Phylogenetics-based analysis revealed that the gut microbiome undergoes a slow but steady recovery in microbial diversity and species richness over a period of a few months following C. difficile therapy. However, in patients who developed recurrent CDI, the recovery of gut microbial diversity and richness was slower and incomplete. There was a paucity of phylotypes within the Lachnospiraceae and Ruminococcaceae family in the Firmicutes Phylum prior to C. difficile recurrence.

Conclusion: These results implicate members of the Lachnospiraceae and Ruminococcaceae family in the pathogenesis of recurrent C. difficile and suggest a potential role in colonization resistance against C. difficile. The organisms identified here may lead to probiotic-based therapy for recurrent C. difficle and the development of a novel diagnostic test for predicting C. difficile recurrence.

Gary Wang, MD, PhD1,2, Eric Li, MS1, Zhubene Mesbah, BS1, Lisa Zhao, MS1, Andrew Kozlov, MD1 and Vijay Antharam, PhD1, (1)Medicine, University of Florida College of Medicine, Gainesville, FL, (2)Medical Service, North Florida/South Georgia Veterans Health System, Gainesville, FL

Disclosures:

G. Wang, Merck: Grant Investigator, Research grant

E. Li, None

Z. Mesbah, None

L. Zhao, None

A. Kozlov, None

V. Antharam, None

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