Journal Article

DKFZ-2025-01076

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Gut microbiota deficiency reduces neutrophil activation and is protective after ischemic stroke.

Tuz, A. A. ; Ghosh, S. ; Karsch, L. ; Antler, M. ; Lakovic, V. ; Lohmann, S. ; Lehmann, A. H. ; Beer, A. ; Nagel, D. ; Jung, M. ; Hörenbaum, N. ; Kaygusuz, V. ; Qefalia, A. ; Alshaar, B. ; Amookazemi, N. ; Bolsega, S. ; Basic, M. ; Siveke, J. T.DKFZ* ; Heiles, S. ; Grüneboom, A. ; Lueong, S.DKFZ* ; Herz, J. ; Sickmann, A. ; Hagemann, N. ; Hasenberg, A. ; Hermann, D. M. ; Gunzer, M. ; Singh, V.

2025
BioMed Central London

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Please use a persistent id in citations: doi:10.1186/s12974-025-03448-w

Abstract: 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.

Keyword(s): Animals (MeSH) ; Gastrointestinal Microbiome: physiology (MeSH) ; Gastrointestinal Microbiome: immunology (MeSH) ; Mice (MeSH) ; Neutrophil Activation: physiology (MeSH) ; Ischemic Stroke: pathology (MeSH) ; Ischemic Stroke: immunology (MeSH) ; Ischemic Stroke: microbiology (MeSH) ; Ischemic Stroke: prevention & control (MeSH) ; Mice, Inbred C57BL (MeSH) ; Male (MeSH) ; Neutrophils (MeSH) ; Germ-Free Life (MeSH) ; Gut microbiota ; Inflammation ; Ischemic stroke ; Neutrophils

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Contributing Institute(s):

1. DKTK Koordinierungsstelle Essen/Düsseldorf (ED01)

Research Program(s):

1. 899 - ohne Topic (POF4-899) (POF4-899)

Appears in the scientific report 2025

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Database coverage:
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