Year: 2025
Type: article
Abstract: ABSTRACT: Prolonged or broad-spectrum antibiotic courses are associated with intestinal dysbiosis and cytopenias, and depletion of hematopoietic progenitor populations after antibiotics is associated with loss of peripheral immune cells, leading to increased susceptibility to systemic infections. We evaluated the bone marrow hematopoietic compartment in a murine model of antibiotic exposure. Single-cell RNA sequencing revealed a substantial and previously unrecognized depletion of bone marrow B cells at all stages of development in antibiotic-treated mice, further confirmed by flow cytometric analysis. Depletion of the microbiota was associated with rapid changes in the peripheral B-cell compartment, yet fecal microbiota transfer did not rescue either peripheral or bone marrow B cells to a greater degree than natural recovery from antibiotic treatment. Antibiotic-mediated loss of B-cell progenitors was secondary to enhanced apoptosis and occurred independent of disrupted systemic type I and II interferon signaling, previously implicated in the maintenance of other hematopoietic compartments. Instead, the depletion of prosurvival MYC signaling was implicated in the depletion of circulating lymphocytes and bone marrow B-cell progenitor populations during antibiotic treatment. Furthermore, in vitro exposure of bone marrow cells to antibiotics demonstrated significantly decreased viability of B cells. We conclude that both microbiota depletion and cytotoxic effects of prolonged broad-spectrum antibiotic treatment disrupt cytokine and cell survival signaling critical for B-cell progenitor maintenance. These results contribute to our understanding of the compartment-specific mechanisms by which the microbiota maintains the hematopoietic system and suggest critical pathways for maintenance of bone marrow progenitors during prolonged antibiotic treatment.
Source: Blood Advances
Authors: Lila S. Sanning, Forrest C. Walker, Arushana A. Maknojia, Leran Wang, Haina Jin, Gowri Kalugotla, Crystal Lovato, Katherine Y. King, Megan T. Baldridge
Language: English
Topic: Gut microbiota and health
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,800
Funders: Cancer Prevention and Research Institute of Texas, Washington University in St. Louis, National Institutes of Health, National Heart, Lung, and Blood Institute, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: BD Biosciences Special Order LSRII, G2859315832, G304139194, G3102002109, G3231407558, Microbiota-dependent regulation of primitive hematopoieses, Training Program in Cellular and Molecular Biology, Advanced Multiparameter Cytometry and Cell Sorting Core, G9000018991, G9000019506, G9000070986, G9000096344, G9000251218, Baylor College of Medicine Cancer Center - Cancer Center Support Grant, Impact of Infection and Inflammation on Primitive Hematopoiesis, Child Health Research Center
OpenAlex ID: W4412480882