Antibiotics impair murine hematopoiesis by depleting the intestinal microbiota

Blood. 2017 Feb 9;129(6):729-739. doi: 10.1182/blood-2016-03-708594. Epub 2016 Nov 22.


Bone marrow suppression is an adverse effect associated with many antibiotics, especially when administered for prolonged treatment courses. Recent advances in our understanding of steady-state hematopoiesis have allowed us to explore the effects of antibiotics on hematopoietic progenitors in detail using a murine model. Antibiotic-treated mice exhibited anemia, thrombocytosis, and leukopenia, with pronounced pan-lymphopenia as demonstrated by flow cytometric analysis of peripheral blood. Bone marrow progenitor analysis revealed depletion of hematopoietic stem cells and multipotent progenitors across all subtypes. Granulocytes and B cells were also diminished in the bone marrow, whereas the number of CD8+ T cells increased. Reductions in progenitor activity were not observed when cells were directly incubated with antibiotics, suggesting that these effects are indirect. Hematopoietic changes were associated with a significant contraction of the fecal microbiome and were partially rescued by fecal microbiota transfer. Further, mice raised in germ-free conditions had hematopoietic abnormalities similar to those seen in antibiotic-treated mice, and antibiotic therapy of germ-free mice caused no additional abnormalities. The effects of antibiotics were phenocopied in Stat1-deficient mice, with no additional suppression by antibiotics in these mice. We conclude that microbiome depletion as a result of broad-spectrum antibiotic treatment disrupts basal Stat1 signaling and alters T-cell homeostasis, leading to impaired progenitor maintenance and granulocyte maturation. Methods to preserve the microbiome may reduce the incidence of antibiotic-associated bone marrow suppression.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anemia / chemically induced*
  • Anemia / microbiology
  • Anemia / pathology
  • Anemia / therapy
  • Animals
  • Anti-Bacterial Agents / adverse effects*
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / metabolism
  • B-Lymphocytes / pathology
  • Bone Marrow Cells / drug effects
  • Bone Marrow Cells / metabolism
  • Bone Marrow Cells / pathology
  • CD8-Positive T-Lymphocytes / drug effects
  • CD8-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / pathology
  • Fecal Microbiota Transplantation
  • Gastrointestinal Microbiome / drug effects*
  • Gastrointestinal Microbiome / physiology
  • Gene Expression
  • Germ-Free Life / drug effects
  • Germ-Free Life / genetics
  • Granulocytes / drug effects
  • Granulocytes / metabolism
  • Granulocytes / pathology
  • Hematopoiesis / drug effects*
  • Hematopoiesis / genetics
  • Hematopoietic Stem Cells / drug effects
  • Hematopoietic Stem Cells / metabolism
  • Hematopoietic Stem Cells / pathology
  • Leukopenia / chemically induced*
  • Leukopenia / microbiology
  • Leukopenia / pathology
  • Leukopenia / therapy
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Macrophages / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • STAT1 Transcription Factor / deficiency
  • STAT1 Transcription Factor / genetics*
  • Signal Transduction
  • Thrombocytosis / chemically induced*
  • Thrombocytosis / microbiology
  • Thrombocytosis / pathology
  • Thrombocytosis / therapy


  • Anti-Bacterial Agents
  • STAT1 Transcription Factor
  • STAT1 protein, human