757. Disordered Distal Gut Microbiota in Clostridium difficile Infection Revealed by High Density Deep Sequencing
Session: Oral Abstract Session: Clostridium difficile: Detection, Transmission, and Treatment
Friday, October 21, 2011: 3:15 PM
Room: 151AB
Background: Clostridium difficile infection (CDI) causes 3 million cases of diarrhea and colitis in the US annually.  The human gut microbiota is widely believed to play an important protective role against CDI, including recurrent disease.  Although the association between perturbation of gut microbiota and CDI is well established, the basic features of gut microbial communities associated with CDI remain poorly understood. 

Methods: We used culture-independent high-density 454 pyrosequencing to assess microbial composition of distal gut microbiota from 39 individuals with CDI, compared with microbial communities from 36 individuals with antibiotic-associated diarrhea (AAD) and 40 healthy controls.

Results: We aligned a total of 555,574 partial (V1-V3) 16S rRNA sequence reads to 16S rRNA databases, identifying 4,174 bacterial phylotypes from 115 fecal samples.  Phylogenetics-based analysis revealed a significant alteration of organism lineages in both the CDI and AAD groups.  The microbial communities in both groups were less diverse and contained fewer phylotypes than the healthy controls.  This decrease in microbial diversity was driven primarily by a paucity of phylotypes within the Firmicutes phylum.  Specifically, members of the Ruminococcaceae and Lachnospiraceae family, including Faecalibacterium spp., Ruminococcus spp., Blautia spp., Subdoligranulum spp. and Collinsella spp. were decreased by 10-35 fold in abundance compared to healthy controls (p < 0.001).  Some of these commensals are butyrate-producing organisms known to play a key role in colonic health, whereas others were recently shown to exert anti-inflammatory activities in the gut.  Surprisingly, the microbial community structures and diversity were indistinguishable between the CDI and the AAD groups.

Conclusion: These findings provide the most detailed sequence-based analysis of gut microbiota associated with CDI to date, and specify characteristic microbial patterns that correlate with host susceptibility to CDI.  These methods should provide a framework for longitudinal analyses of the temporal response of gut microbial communities to C. difficile therapy and their relationship to recurrent disease, which is a major problem facing many patients today.


Subject Category: B. Bacterial pathogenesis, studies in animal models, molecular pathogenicity

Vijay Antharam, PhD1, Eric Li, MS1, Arif Ishmael, MD1, Anuj Sharma, MD1, Volker Mai, PhD2, Kenneth Rand, MD3 and Gary Wang, MD, PhD1, (1)Medicine, University of Florida College of Medicine, Gainesville, FL, (2)Microbiology and Cell Science, University of Florida College of Agricultural and Life Sciences, Gainesville, FL, (3)Pathology, University of Florida College of Medicine, Gainesville, FL

Disclosures:

V. Antharam, None

E. Li, None

A. Ishmael, None

A. Sharma, None

V. Mai, None

K. Rand, bioMeriuex : Consultant, Consulting fee and Speaker honorarium
Idaho Technology: Consultant, Consulting fee, Grant recipient and Research grant

G. Wang, None

Findings in the abstracts are embargoed until 12:01 a.m. EST Thursday, Oct. 20 with the exception of research findings presented at IDSA press conferences.