Alterations in the Gut Microbiome in Recurrent Clostridium difficile Infection
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.
Merck: Grant Investigator, Research grant
Z. Mesbah, None
L. Zhao, None
A. Kozlov, None
V. Antharam, None