2227.  What’s in the Box? – Investigation into Why Dirty Cages from Young Mice Can Save Aged Mice with C. difficile Infection
Session: Poster Abstract Session: Microbiome: GI
Saturday, October 29, 2016
Room: Poster Hall
Posters
  • JaeShin.pdf (1.8 MB)
  • Background:

    Clostridium difficileinfection (CDI) leads to more severe disease and death in the aging population. We used various methods to identify the change in microbiota affecting immune response and outcome with an aged mouse model of CDI.

    Methods:

    Young (8 weeks) and aged (18 months) mice were infected with C. difficileafter antibiotic exposure and monitored for mortality and disease. In a follow up experiment dirty cages of young and aged mice were exchanged every 2 days to mix the intestinal microbiota. Stool samples were collected at baseline, after cage exchange, after antibiotic exposure, and after infection. Fecal microbiome was amplified by PCR with primers for V1-V3 hypervariable regions of 16S rRNA gene then quantified by 16S Illumina MiSeq sequencing.

    Results:

    Outcome was significantly worse in aged mice compared to young mice, with higher mortality, worse diarrhea and weight loss. With cage exchange, mortality in aged mice improved dramatically to the level of young mice.

    Preliminary analysis of phylum level composition showed that the microbiota at baseline was highly variable between experiments and even between individual mice within the same age group. On the other hand, within each group, interventions such as cage exchange, antibiotic exposure and CDI did not greatly alter the composition of the microbiota despite differences in clinical outcomes.

    Conclusion:

    Aged mouse model of CDI demonstrates the effect of aging on clinical outcome which can be reversed with cage switching. Our preliminary microbiome analysis showed wide baseline variability at baseline without significant change with manipulation. This suggests that changes resulting from microbiota modulation may not be detected with conventional broad range analysis of the microbiome. Further studies into specific candidate species, functional genomics or metabolomics may be more informative. Alternatively, alteration of intestinal microbiota may not completely explain effects of aging on susceptibility to severe disease in CDI.

    Jae Hyun Shin, MD, David Bolick, MS and Cirle Warren, MD, Division of Infectious Diseases and International Health, University of Virginia, Charlottesville, VA

    Disclosures:

    J. H. Shin, None

    D. Bolick, None

    C. Warren, None

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