Journal of Neuroinflammation (May 2025)
Gut microbiota deficiency reduces neutrophil activation and is protective after ischemic stroke
- Ali A. Tuz,
- Susmita Ghosh,
- Laura Karsch,
- Medina Antler,
- Vivian Lakovic,
- Sabrina Lohmann,
- Amber Hope Lehmann,
- Alexander Beer,
- Dennis Nagel,
- Marcel Jung,
- Nils Hörenbaum,
- Viola Kaygusuz,
- Altea Qefalia,
- Belal Alshaar,
- Niloufar Amookazemi,
- Silvia Bolsega,
- Marijana Basic,
- Jens T. Siveke,
- Sven Heiles,
- Anika Grüneboom,
- Smiths Lueong,
- Josephine Herz,
- Albert Sickmann,
- Nina Hagemann,
- Anja Hasenberg,
- Dirk M. Hermann,
- Matthias Gunzer,
- Vikramjeet Singh
Affiliations
- Ali A. Tuz
- Institute for Experimental Immunology and Imaging, University Hospital Essen, University of Duisburg-Essen
- Susmita Ghosh
- Leibniz-Institut Für Analytische Wissenschaften - ISAS - E.V.
- Laura Karsch
- Institute for Experimental Immunology and Imaging, University Hospital Essen, University of Duisburg-Essen
- Medina Antler
- Institute for Experimental Immunology and Imaging, University Hospital Essen, University of Duisburg-Essen
- Vivian Lakovic
- Institute for Experimental Immunology and Imaging, University Hospital Essen, University of Duisburg-Essen
- Sabrina Lohmann
- Institute for Experimental Immunology and Imaging, University Hospital Essen, University of Duisburg-Essen
- Amber Hope Lehmann
- Institute for Experimental Immunology and Imaging, University Hospital Essen, University of Duisburg-Essen
- Alexander Beer
- Institute for Experimental Immunology and Imaging, University Hospital Essen, University of Duisburg-Essen
- Dennis Nagel
- Institute for Experimental Immunology and Imaging, University Hospital Essen, University of Duisburg-Essen
- Marcel Jung
- Institute for Experimental Immunology and Imaging, University Hospital Essen, University of Duisburg-Essen
- Nils Hörenbaum
- Institute for Experimental Immunology and Imaging, University Hospital Essen, University of Duisburg-Essen
- Viola Kaygusuz
- Institute for Experimental Immunology and Imaging, University Hospital Essen, University of Duisburg-Essen
- Altea Qefalia
- Institute for Experimental Immunology and Imaging, University Hospital Essen, University of Duisburg-Essen
- Belal Alshaar
- Leibniz-Institut Für Analytische Wissenschaften - ISAS - E.V.
- Niloufar Amookazemi
- Institute for Experimental Immunology and Imaging, University Hospital Essen, University of Duisburg-Essen
- Silvia Bolsega
- Institute for Laboratory Animal Science and Central Animal Facility, Hannover Medical School
- Marijana Basic
- Institute for Laboratory Animal Science and Central Animal Facility, Hannover Medical School
- Jens T. Siveke
- Division of Solid Tumor Translational Oncology, German Cancer Consortium (DKTK, Partner Site Essen), German Cancer Research Center (DKFZ)
- Sven Heiles
- Leibniz-Institut Für Analytische Wissenschaften - ISAS - E.V.
- Anika Grüneboom
- Leibniz-Institut Für Analytische Wissenschaften - ISAS - E.V.
- Smiths Lueong
- Division of Solid Tumor Translational Oncology, German Cancer Consortium (DKTK, Partner Site Essen), German Cancer Research Center (DKFZ)
- Josephine Herz
- Department of Pediatrics I, Neonatology and Experimental Perinatal Neurosciences, and Center for Translational Neuro- and Behavioral Sciences (C-TNBS), University Hospital Essen, University of Duisburg-Essen
- Albert Sickmann
- Leibniz-Institut Für Analytische Wissenschaften - ISAS - E.V.
- Nina Hagemann
- Department of Neurology, University Hospital Essen, University of Duisburg-Essen
- Anja Hasenberg
- Institute for Experimental Immunology and Imaging, University Hospital Essen, University of Duisburg-Essen
- Dirk M. Hermann
- Department of Neurology, University Hospital Essen, University of Duisburg-Essen
- Matthias Gunzer
- Institute for Experimental Immunology and Imaging, University Hospital Essen, University of Duisburg-Essen
- Vikramjeet Singh
- Institute for Experimental Immunology and Imaging, University Hospital Essen, University of Duisburg-Essen
- DOI
- https://doi.org/10.1186/s12974-025-03448-w
- Journal volume & issue
-
Vol. 22,
no. 1
pp. 1 – 13
Abstract
Summary Neutrophils are readily activated immune cells after ischemic stroke in mice and patients. Still, the impact of gut microbiota on neutrophil activation and its influence on inflammatory brain injury remain undefined. We report that natural microbiota colonization of germ-free (GF) mice induces substantial neutrophil activation and deteriorates stroke pathology. The colonized Ex-GF stroke mice had considerably larger infarct sizes and higher sensorimotor deficits than GF littermates. Furthermore, employing an antibiotic-based mouse model of microbiota deficiency, we demonstrate that gut microbiota depletion induces a juvenile neutrophil phenotype characterized by the upregulation of resting state surface receptors, reduced inflammatory proteins, and levels of circulating NETs. This disarming of neutrophil responses was associated with decreased expression of brain inflammatory genes, vascular thrombus formation, reduced infarct size, and alleviated behavioral deficits. We conclude that gut microbes strongly influence neutrophil activation after stroke and thus directly contribute to stroke severity.
Keywords
