Gut microbiota deficiency reduces neutrophil activation and is protective after ischemic stroke
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.
Authors
- Smiths Lueong (ORCID: https://orcid.org/0000-0002-2776-6706)
- A. Lehmann
- Sabrina Lohmann (ORCID: https://orcid.org/0000-0002-0635-3785)
- Viola Kaygusuz
- Josephine Herz (ORCID: https://orcid.org/0000-0001-8132-7459)
- Vivian Lakovic
- Matthias Gunzer (ORCID: https://orcid.org/0000-0002-5534-6055)
- Marijana Basic (ORCID: https://orcid.org/0000-0002-1995-618X)
- Albert Sickmann (ORCID: https://orcid.org/0000-0002-2388-5265)
- Sven Heiles (ORCID: https://orcid.org/0000-0003-3779-8071)
- Ali Ata Tuz (ORCID: https://orcid.org/0000-0002-9802-2317)
- Dirk M. Hermann (ORCID: https://orcid.org/0000-0003-0198-3152)
- Marcel Jung (ORCID: https://orcid.org/0000-0002-8277-3052)
- Nina Hagemann (ORCID: https://orcid.org/0000-0002-8098-0402)
- Medina Antler
- Jens Thomas Siveke (ORCID: https://orcid.org/0000-0002-8772-4778)
- Anika Grüneboom (ORCID: https://orcid.org/0000-0002-7928-5613)
- Altea Qefalia
- Alexander Beer
- Silvia Bolsega
- Anja Hasenberg (ORCID: https://orcid.org/0000-0002-4468-6361)
- Vikramjeet Singh (ORCID: https://orcid.org/0000-0002-7361-8317)
- Susmita Ghosh (ORCID: https://orcid.org/0000-0001-9798-0989)
- Laura Karsch (ORCID: https://orcid.org/0009-0000-4759-9178)
- Dennis Nagel (ORCID: https://orcid.org/0009-0004-2911-9301)
- Belal Alshaar
- Nils Hörenbaum
- Niloufar Amookazemi
Institutions
- German Cancer Research Center (DE)
- Heidelberg University (DE)
- University Hospitals of the Ruhr-University of Bochum (DE)
- Medizinische Hochschule Hannover (DE)
- Essen University Hospital (DE)
- Leibniz Institute for Analytical Sciences - ISAS (DE)
- University of Duisburg-Essen (DE)
- Ruhr University Bochum (DE)
Publication Details
- Journal
- Journal of Neuroinflammation
- Published
- 2025-05-23
- DOI
- https://doi.org/10.1186/s12974-025-03448-w
- Citations
- 4
- Primary Topic
- Neuroinflammation and Neurodegeneration Mechanisms
- Type
- article
- Field-Weighted Citation Impact
- 3.37
Funders
- Universitätsklinikum Essen
- Deutsche Forschungsgemeinschaft