Neuroprotective Effect of β‐1,3‐Glucans‐Rich <i>Euglena gracilis</i> Against Ischemic Stroke in Middle‐Aged Mice Fed With a High‐Fat‐High‐Fructose Diet

Ischemic stroke leads to significant neurological deficits and remains a leading cause of disability and mortality worldwide. β-1,3-glucans-rich Euglena gracilis (EG), a type of dietary supplement, was reported to regulate metabolic perturbation and the gut-brain axis that have been implicated in aggravation of the disease. The present study aimed to investigate the neuroprotective effects of EG supplementation in an ischemic stroke model in middle-aged mice fed with a high-fat high-fructose (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-chain fatty acid production. Our results suggest that EG supplementation may be a promising dietary strategy to mitigate HFHF diet-induced exacerbation of ischemic stroke via the gut-brain axis.