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
{"title":"肠道菌群缺乏可减少中性粒细胞活化,并在缺血性中风后起到保护作用。","authors":"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","doi":"10.1186/s12974-025-03448-w","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":16577,"journal":{"name":"Journal of Neuroinflammation","volume":"22 1","pages":"137"},"PeriodicalIF":10.1000,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12100894/pdf/","citationCount":"0","resultStr":"{\"title\":\"Gut microbiota deficiency reduces neutrophil activation and is protective after ischemic stroke.\",\"authors\":\"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\",\"doi\":\"10.1186/s12974-025-03448-w\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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.</p>\",\"PeriodicalId\":16577,\"journal\":{\"name\":\"Journal of Neuroinflammation\",\"volume\":\"22 1\",\"pages\":\"137\"},\"PeriodicalIF\":10.1000,\"publicationDate\":\"2025-05-23\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12100894/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Neuroinflammation\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1186/s12974-025-03448-w\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Neuroinflammation","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s12974-025-03448-w","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
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.
期刊介绍:
The Journal of Neuroinflammation is a peer-reviewed, open access publication that emphasizes the interaction between the immune system, particularly the innate immune system, and the nervous system. It covers various aspects, including the involvement of CNS immune mediators like microglia and astrocytes, the cytokines and chemokines they produce, and the influence of peripheral neuro-immune interactions, T cells, monocytes, complement proteins, acute phase proteins, oxidative injury, and related molecular processes.
Neuroinflammation is a rapidly expanding field that has significantly enhanced our knowledge of chronic neurological diseases. It attracts researchers from diverse disciplines such as pathology, biochemistry, molecular biology, genetics, clinical medicine, and epidemiology. Substantial contributions to this field have been made through studies involving populations, patients, postmortem tissues, animal models, and in vitro systems.
The Journal of Neuroinflammation consolidates research that centers around common pathogenic processes. It serves as a platform for integrative reviews and commentaries in this field.