{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T15:05:17Z","timestamp":1782745517828,"version":"3.54.5"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,5,9]],"date-time":"2023-05-09T00:00:00Z","timestamp":1683590400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Gut microbiota affects the gut\u2013brain axis; hence, the modulation of the microbiota has been proposed as a potential therapeutic strategy for cerebral ischemia\/reperfusion injury (CIRI). However, the role and mechanism of the gut microbiota in regulating microglial polarization during CIRI remain poorly understood. Herein, using a middle cerebral artery occlusion and reperfusion (MCAO\/R) rat model, we evaluated changes in the gut microbiota after CIRI and the potential effects of fecal microbiota transplant (FMT) on the brain. Rats underwent either MCAO\/R or sham surgery, and then they received FMT (started 3\u00a0days later; continued for 10\u00a0days). 2,3,5-Triphenyltetrazolium chloride staining, neurological outcome scale, and Fluoro-Jade C staining showed that MCAO\/R induced cerebral infarction, neurological deficits, and neuronal degeneration. In addition, immunohistochemistry or real-time PCR assay showed increased expression levels of M1-macrophage markers\u2014TNF-\u03b1, IL-1\u03b2, IL-6, and iNOS\u2014in the rats following MCAO\/R. Our finding suggests that microglial M1 polarization is involved in CIRI. 16\u00a0S ribosomal RNA gene sequencing data revealed an imbalance in the gut microbiota of MCAO\/R animals. In contrast, FMT reversed this MCAO\/R-induced imbalance in the gut microbiota and ameliorated nerve injury. In addition, FMT prevented the upregulation in the ERK and NF-\u03baB pathways, which reversed the M2-to-M1 microglial shift 10\u00a0days after MCAO\/R injury in rats. Our primary data showed that the modulation of the gut microbiota can attenuate CIRI in rats by inhibiting microglial M1 polarization through the ERK and NF-\u03baB pathways. However, an understanding of the underlying mechanism requires further study.<\/jats:p>","DOI":"10.3389\/fphar.2023.1123387","type":"journal-article","created":{"date-parts":[[2023,5,9]],"date-time":"2023-05-09T05:10:11Z","timestamp":1683609011000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["Modulation of gut microbiota alleviates cerebral ischemia\/reperfusion injury in rats by inhibiting M1 polarization of microglia"],"prefix":"10.3389","volume":"14","author":[{"given":"Hai-Jun","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan-Qing","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Liang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Fei","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hai-Tao","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li-Xia","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guang","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,5,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"770017","DOI":"10.3389\/fmed.2022.770017","article-title":"Refining a protocol for faecal microbiota engraftment in animal models after successful antibiotic-induced gut decontamination","volume":"9","author":"Amorim","year":"2022","journal-title":"Front. 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