***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.

***Disclosures.*** **G. Wang**, Merck: Grant Investigator, Research grant

[^1]: **Session:** 24. Bacterial Pathogenesis

[^2]: Thursday, October 9, 2014: 8:30 AM
