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This study aimed to investigate whether shifts in gut microbiota are associated with concurrent changes in lipopolysaccharide (LPS) levels and neuroinflammatory responses following ischemic stroke. Methods: Using a photothrombotic mouse model, we measured LPS in the gut, serum, and brain via ELISA and immunohistochemistry. Gentamycin was administered to deplete gut bacteria and assess its effects on LPS and stroke recovery. Upon TLR4 inhibition with TAK-242, microglial polarization and inflammatory cytokines were evaluated, and dose-dependent LPS supplementation was performed. Results: Ischemic stroke was accompanied by elevated LPS levels in the gut, circulation, and brain, paralleling Verrucomicrobiota expansion. Antibiotic treatment reduced Verrucomicrobiota and LPS in the gut and brain, and this was associated with worsened stroke outcomes. TLR4 inhibition was associated with altered microglial phenotypes and inflammatory markers. Exogenous LPS produced dose-dependent effects, whereas endogenous LPS levels remained low. Conclusions: These findings reveal a spatial correlation between gut microbial shifts, circulating LPS, and cerebral LPS immunoreactivity, suggesting LPS may serve as a correlative marker of gut\u2013brain interactions following ischemic stroke.<\/jats:p>","DOI":"10.3390\/cells15191819","type":"journal-article","created":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T16:21:46Z","timestamp":1791303706000},"page":"1819","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Correlation Between Gut Microbiota Shifts, Lipopolysaccharide Levels, and Neuroinflammatory Responses Following Ischemic Stroke"],"prefix":"10.3390","volume":"15","author":[{"given":"Kemin","family":"Li","sequence":"first","affiliation":[{"name":"School of Food Science and Engineering, Xinjiang Institute of Technology, No. 1 Xuefu Road West, Aksu 843100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wancong","family":"Ding","sequence":"additional","affiliation":[{"name":"Gansu Key Laboratory of Biomonitoring and Bioremediation for Environmental Pollution, School of Life Sciences, Lanzhou University, No. 222 South Tianshui Road, Lanzhou 730000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuang","family":"Wang","sequence":"additional","affiliation":[{"name":"Gansu Key Laboratory of Biomonitoring and Bioremediation for Environmental Pollution, School of Life Sciences, Lanzhou University, No. 222 South Tianshui Road, Lanzhou 730000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaowei","family":"Pan","sequence":"additional","affiliation":[{"name":"Gansu Key Laboratory of Biomonitoring and Bioremediation for Environmental Pollution, School of Life Sciences, Lanzhou University, No. 222 South Tianshui Road, Lanzhou 730000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6524-9673","authenticated-orcid":false,"given":"Shengxiang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Gansu Key Laboratory of Biomonitoring and Bioremediation for Environmental Pollution, School of Life Sciences, Lanzhou University, No. 222 South Tianshui Road, Lanzhou 730000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,10,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Maida, C.D., Norrito, R.L., Daidone, M., Tuttolomondo, A., and Pinto, A. 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