887. Antibiotics Cause Multilineage Alteration of Hematopoiesis in Mice
Session: Poster Abstract Session: Biomarkers and Adverse Events
Friday, October 9, 2015
Room: Poster Hall
Posters
  • 887_Josefsdottir.png (184.3 kB)
  • Background:

    Immune and inflammatory processes play a role in the regulation of hematopoiesis. For instance, germ free mice have abnormal hematopoiesis that can be normalized by introduction of a diverse microbiome. Furthermore, bone marrow suppression is a known complication of antibiotic therapy, particularly beta-lactams. We hypothesize that antibiotic therapy suppresses hematopoiesis by altering inflammatory tone through effects on the microbiome. The goal of this study is to establish a mouse model of antibiotic-induced myelosuppression and identify the mechanism by which this complication occurs.

    Methods:

    Mice were fed water containing flavored antibiotics or flavoring alone for 14 days. Blood and bone marrow were analyzed by flow cytometry. Colony formation and competitive transplant assays were used to functionally assess bone marrow progenitors. 16S rDNA sequencing was performed on stool for microbiome characterization.

    Results:

    Mice treated with antibiotics were leukopenic, anemic and had involution of lymphoid tissues. They exhibited slow intestinal transit and reduced microbial diversity. Analysis of marrow revealed decreased cellularity, with few B cells and neutrophils, but increased T cells. Stem cell and myeloid-committed progenitor populations were conserved, but uncommited primitive and lymphoid progenitor populations were depleted. Marrow from treated mice showed increased colony formation, but decreased myeloid output after transplantation.

    Conclusion:

    Broad-spectrum antibiotics cause multilineage abnormalities in hematopoiesis in mice after only two weeks. Our results suggest that antibiotic treatment leads to T cell infiltration into bone marrow, and depletion of primitive progenitors with permanent implications as seen in transplant assays. We will use this model to assess whether microbiome shifts induce changes in basal inflammatory tone and progenitor function. Delineation of this process could lead to development of therapies to counteract myelosuppression with antibiotic use.

    Kamilla Josefsdottir, M.D.1, Megan Baldridge, M.D., Ph.D.2, Herbert Virgin, M.D., Ph.D.2 and Katherine King, M.D. Ph.D.1, (1)Pediatric Infectious Diseases, Baylor College of Medicine, Houston, TX, (2)Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO

    Disclosures:

    K. Josefsdottir, None

    M. Baldridge, None

    H. Virgin, None

    K. King, None

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