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The bacterial microbiota regulates normal hematopoiesis via metabolite-induced type 1 interferon signaling
Antibiotic therapy, especially when administered long term, is associated with adverse hematologic effects such as cytopenia. Signals from the intestinal microbiota are critical to maintain normal hematopoiesis, and antibiotics can cause bone marrow suppression through depletion of the microbiota. W...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society of Hematology
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8941453/ https://www.ncbi.nlm.nih.gov/pubmed/35143611 http://dx.doi.org/10.1182/bloodadvances.2021006816 |
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author | Yan, Hannah Walker, Forrest C. Ali, Arushana Han, Hyojeong Tan, Lin Veillon, Lucas Lorenzi, Philip L. Baldridge, Megan T. King, Katherine Y. |
author_facet | Yan, Hannah Walker, Forrest C. Ali, Arushana Han, Hyojeong Tan, Lin Veillon, Lucas Lorenzi, Philip L. Baldridge, Megan T. King, Katherine Y. |
author_sort | Yan, Hannah |
collection | PubMed |
description | Antibiotic therapy, especially when administered long term, is associated with adverse hematologic effects such as cytopenia. Signals from the intestinal microbiota are critical to maintain normal hematopoiesis, and antibiotics can cause bone marrow suppression through depletion of the microbiota. We reported previously that STAT1 signaling is necessary for microbiota-dependent hematopoiesis, but the precise mechanisms by which the gut microbiota signals to the host bone marrow to regulate hematopoiesis remain undefined. We sought to identify the cell type(s) through which STAT1 promotes microbiota-mediated hematopoiesis and to elucidate which upstream signaling pathways trigger STAT1 signaling. Using conditional knockout and chimeric mice, we found that the microbiota induced STAT1 signaling in non-myeloid hematopoietic cells to support hematopoiesis and that STAT1 signaling was specifically dependent on type I interferons (IFNs). Indeed, basal type I IFN signaling was reduced in hematopoietic progenitor cells with antibiotic treatment. In addition, we discovered that oral administration of a commensal-derived product, NOD1 ligand, rescues the hematopoietic defects induced by antibiotics in mice. Using metabolomics, we identified additional microbially produced candidates that can stimulate type I IFN signaling to potentially rescue the hematopoietic defects induced by antibiotics, including phosphatidylcholine and γ-glutamylalanine. Overall, our studies define a signaling pathway through which microbiota promotes normal hematopoiesis and identify microbial metabolites that may serve as therapeutic agents to ameliorate antibiotic-induced bone marrow suppression and cytopenia. |
format | Online Article Text |
id | pubmed-8941453 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Society of Hematology |
record_format | MEDLINE/PubMed |
spelling | pubmed-89414532022-03-29 The bacterial microbiota regulates normal hematopoiesis via metabolite-induced type 1 interferon signaling Yan, Hannah Walker, Forrest C. Ali, Arushana Han, Hyojeong Tan, Lin Veillon, Lucas Lorenzi, Philip L. Baldridge, Megan T. King, Katherine Y. Blood Adv Hematopoiesis and Stem Cells Antibiotic therapy, especially when administered long term, is associated with adverse hematologic effects such as cytopenia. Signals from the intestinal microbiota are critical to maintain normal hematopoiesis, and antibiotics can cause bone marrow suppression through depletion of the microbiota. We reported previously that STAT1 signaling is necessary for microbiota-dependent hematopoiesis, but the precise mechanisms by which the gut microbiota signals to the host bone marrow to regulate hematopoiesis remain undefined. We sought to identify the cell type(s) through which STAT1 promotes microbiota-mediated hematopoiesis and to elucidate which upstream signaling pathways trigger STAT1 signaling. Using conditional knockout and chimeric mice, we found that the microbiota induced STAT1 signaling in non-myeloid hematopoietic cells to support hematopoiesis and that STAT1 signaling was specifically dependent on type I interferons (IFNs). Indeed, basal type I IFN signaling was reduced in hematopoietic progenitor cells with antibiotic treatment. In addition, we discovered that oral administration of a commensal-derived product, NOD1 ligand, rescues the hematopoietic defects induced by antibiotics in mice. Using metabolomics, we identified additional microbially produced candidates that can stimulate type I IFN signaling to potentially rescue the hematopoietic defects induced by antibiotics, including phosphatidylcholine and γ-glutamylalanine. Overall, our studies define a signaling pathway through which microbiota promotes normal hematopoiesis and identify microbial metabolites that may serve as therapeutic agents to ameliorate antibiotic-induced bone marrow suppression and cytopenia. American Society of Hematology 2022-03-15 /pmc/articles/PMC8941453/ /pubmed/35143611 http://dx.doi.org/10.1182/bloodadvances.2021006816 Text en © 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved. |
spellingShingle | Hematopoiesis and Stem Cells Yan, Hannah Walker, Forrest C. Ali, Arushana Han, Hyojeong Tan, Lin Veillon, Lucas Lorenzi, Philip L. Baldridge, Megan T. King, Katherine Y. The bacterial microbiota regulates normal hematopoiesis via metabolite-induced type 1 interferon signaling |
title | The bacterial microbiota regulates normal hematopoiesis via metabolite-induced type 1 interferon signaling |
title_full | The bacterial microbiota regulates normal hematopoiesis via metabolite-induced type 1 interferon signaling |
title_fullStr | The bacterial microbiota regulates normal hematopoiesis via metabolite-induced type 1 interferon signaling |
title_full_unstemmed | The bacterial microbiota regulates normal hematopoiesis via metabolite-induced type 1 interferon signaling |
title_short | The bacterial microbiota regulates normal hematopoiesis via metabolite-induced type 1 interferon signaling |
title_sort | bacterial microbiota regulates normal hematopoiesis via metabolite-induced type 1 interferon signaling |
topic | Hematopoiesis and Stem Cells |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8941453/ https://www.ncbi.nlm.nih.gov/pubmed/35143611 http://dx.doi.org/10.1182/bloodadvances.2021006816 |
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