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The present study aimed to investigate the neuroprotective effects of EG supplementation in an ischemic stroke model in middle\u2010aged mice fed with a high\u2010fat high\u2010fructose (HFHF) diet. The mice were divided into three groups: HFHF, HFHF+EG (HFHF_EG), and HFHF+Sham (HFHF_Sham). After 8 weeks of dietary intervention, ischemic stroke was induced via middle cerebral artery occlusion (MCAO) in the HFHF and HFHF_EG groups. The data revealed that EG supplementation significantly reduced infarct volume, alleviated neurological deficits, and enhanced synaptic plasticity in the hippocampus. The neuroprotective effects of EG were associated with improved intestinal barrier integrity, reduced systemic and neuroinflammation, and modulation of the hippocampal insulin signaling pathway. Furthermore, EG supplementation favorably altered gut microbiota composition, especially enhancing the relative abundance of beneficial bacteria and short\u2010chain fatty acid production. Our results suggest that EG supplementation may be a promising dietary strategy to mitigate HFHF diet\u2010induced exacerbation of ischemic stroke via the gut\u2010brain axis.<\/jats:p>","DOI":"10.1002\/mnfr.70084","type":"journal-article","created":{"date-parts":[[2025,5,19]],"date-time":"2025-05-19T03:25:54Z","timestamp":1747625154000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Neuroprotective Effect of \u03b2\u20101,3\u2010Glucans\u2010Rich <i>Euglena gracilis<\/i> Against Ischemic Stroke in Middle\u2010Aged Mice Fed With a High\u2010Fat\u2010High\u2010Fructose Diet"],"prefix":"10.1002","volume":"69","author":[{"given":"Haoxie","family":"Xu","sequence":"first","affiliation":[{"name":"Institute for Advanced Study Shenzhen University  Shenzhen China"},{"name":"Department of Food Science and Engineering, College of Chemistry and Environmental Engineering Shenzhen University  Shenzhen China"},{"name":"Institute 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