Tuz Ali A, Ghosh Susmita, Karsch Laura, Antler Medina, Lakovic Vivian, Lohmann Sabrina, Lehmann Amber Hope, Beer Alexander, Nagel Dennis, Jung Marcel, Hörenbaum Nils, Kaygusuz Viola, Qefalia Altea, Alshaar Belal, Amookazemi Niloufar, Bolsega Silvia, Basic Marijana, Siveke Jens T, Heiles Sven, Grüneboom Anika, Lueong Smiths, Herz Josephine, Sickmann Albert, Hagemann Nina, Hasenberg Anja, Hermann Dirk M, Gunzer Matthias, Singh Vikramjeet
Institute for Experimental Immunology and Imaging, University Hospital Essen, University of Duisburg-Essen, 45147, Essen, Germany.
Leibniz-Institut Für Analytische Wissenschaften - ISAS - E.V., 44139, Dortmund, Germany.
J Neuroinflammation. 2025 May 23;22(1):137. doi: 10.1186/s12974-025-03448-w.
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.
在小鼠和患者中，中性粒细胞是缺血性中风后容易被激活的免疫细胞。然而，肠道微生物群对中性粒细胞激活的影响及其对炎症性脑损伤的作用仍不明确。我们报告称，无菌（GF）小鼠的自然微生物群定殖会诱导大量中性粒细胞激活，并使中风病理恶化。与GF同窝小鼠相比，定殖后的Ex-GF中风小鼠的梗死面积明显更大，感觉运动功能缺损更严重。此外，利用基于抗生素的微生物群缺乏小鼠模型，我们证明肠道微生物群耗竭会诱导一种幼稚中性粒细胞表型，其特征是静息状态表面受体上调、炎症蛋白减少以及循环中性粒细胞胞外陷阱（NETs）水平降低。中性粒细胞反应的这种减弱与脑炎症基因表达降低、血管血栓形成减少、梗死面积减小以及行为缺陷减轻有关。我们得出结论，肠道微生物对中风后中性粒细胞激活有强烈影响，从而直接影响中风严重程度。
