922. Microbial Regulation of Mucosal Immune System of mice Exposed to Sub-therapeutic Antibiotic Treatment (STAT)
Session: Poster Abstract Session: Bacterial Pathogenesis
Saturday, October 22, 2011
Room: Poster Hall B1
Handouts
  • Poster for IDSA Shingo Yamanishi.pdf (521.1 kB)
  • Background: The intestinal microbiota functions not only in digestion and metabolism, but also in regulation of the immune system. Thus, an imbalance in microbial composition may cause irregularities in both metabolism and immunity. The incidence of chronic inflammatory diseases such as inflammatory bowel disease (IBD), obesity, type 1 diabetes mellitus, and asthma has increased in developed countries in recent decades; this may be attributed to changes in intestinal contents due to diet and/or antibiotic use. We hypothesized that alterations in the intestinal microbiota may lead to variation in immune responses. 

    Methods: For this study, we developed a mouse model by providing continuous, sub-therapeutic antibiotic treatment (STAT) to young animals. We found both a higher level of adiposity and alterations in intestinal microbiota in the STAT mice compared to controls. To evaluate proportions and cytokine profiles of helper T cells, that play a central role in regulating both innate and acquired immunity, we quantitated expression of helper T-cell regulatory transcriptional factors and their characteristic cytokines by qPCR.

    Results: At 20 weeks, STAT mice (n=10) exhibited significantly higher expression of GATA3 and IL-4 (Th2), Foxp3 and TGF-β (Treg) in the distal ileum compared to control mice (n=8) (p<0.05). The STAT mice had significantly decreased β-defensin 1 (p=0.02) and lower expression of IL-17A and IL-17F compared to controls. 

    Conclusion: These data suggest that STAT increases Th2 and Treg cell number and decreases cytokine production by Th17 cells and downstream β-defensin 1 production. In total, these findings indicate that alterations in intestinal microbial composition by STAT exposure lead to changes in intestinal helper T-cell proportions. Although Th17 cells have pro-inflammatory functions, they also are involved in the maintenance of the intestinal mucosal barrier by regulating production of antimicrobial peptides. Down-regulation of β-defensin 1, possibly due to decreased IL-17 (A and F) production, may impair mucosal barrier function with subsequent impact on adiposity.


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

    Shingo Yamanishi, MD, Ph.D., Medicine, New York University Langone Medical Center, New York, NY, Laura Cox, Microbiology, New York University Medical Center, New York, NY and Martin Blaser, MD, FIDSA, Department of Medicine, New York University School of Medicine, New York, NY

    Disclosures:

    S. Yamanishi, None

    L. Cox, None

    M. Blaser, 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.