TY  - JOUR
AU  - Tuz, Ali A
AU  - Ghosh, Susmita
AU  - Karsch, Laura
AU  - Antler, Medina
AU  - Lakovic, Vivian
AU  - Lohmann, Sabrina
AU  - Lehmann, Amber Hope
AU  - Beer, Alexander
AU  - Nagel, Dennis
AU  - Jung, Marcel
AU  - Hörenbaum, Nils
AU  - Kaygusuz, Viola
AU  - Qefalia, Altea
AU  - Alshaar, Belal
AU  - Amookazemi, Niloufar
AU  - Bolsega, Silvia
AU  - Basic, Marijana
AU  - Siveke, Jens T
AU  - Heiles, Sven
AU  - Grüneboom, Anika
AU  - Lueong, Smiths
AU  - Herz, Josephine
AU  - Sickmann, Albert
AU  - Hagemann, Nina
AU  - Hasenberg, Anja
AU  - Hermann, Dirk M
AU  - Gunzer, Matthias
AU  - Singh, Vikramjeet
TI  - Gut microbiota deficiency reduces neutrophil activation and is protective after ischemic stroke.
JO  - Journal of neuroinflammation
VL  - 22
IS  - 1
SN  - 1742-2094
CY  - London
PB  - BioMed Central
M1  - DKFZ-2025-01076
SP  - 137
PY  - 2025
AB  - 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.
KW  - Animals
KW  - Gastrointestinal Microbiome: physiology
KW  - Gastrointestinal Microbiome: immunology
KW  - Mice
KW  - Neutrophil Activation: physiology
KW  - Ischemic Stroke: pathology
KW  - Ischemic Stroke: immunology
KW  - Ischemic Stroke: microbiology
KW  - Ischemic Stroke: prevention & control
KW  - Mice, Inbred C57BL
KW  - Male
KW  - Neutrophils
KW  - Germ-Free Life
KW  - Gut microbiota (Other)
KW  - Inflammation (Other)
KW  - Ischemic stroke (Other)
KW  - Neutrophils (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:40410847
C2  - pmc:PMC12100894
DO  - DOI:10.1186/s12974-025-03448-w
UR  - https://inrepo02.dkfz.de/record/301568
ER  -