Dietary Supplementation with Nervonic Acid Ameliorates Cerebral Ischemia‐Reperfusion Injury by Modulating of Gut Microbiota Composition‐Fecal Metabolites Interaction

Scope Cerebral ischemia‐reperfusion (IR) injury stands as a prominent global contributor to disability and mortality. Nervonic acid (NA), a bioactive elongated monounsaturated fatty acid, holds pivotal significance in human physiological well‐being. This research aims to explore the prophylactic effects and fundamental mechanisms of NA in a rat model of cerebral IR injury. Methods and results Through the induction of middle cerebral artery occlusion, this study establishes a rat model of cerebral IR injury and comprehensively assesses the pharmacodynamic impacts of NA pretreatment. This evaluation involves behavioral analyses, histopathological examinations, and quantification of serum markers. Detailed mechanisms of nervonic acid's prophylactic effects are revealed through fecal metabolomics and 16S rRNA sequencing analyses. Our findings robustly support nervonic acid's capacity to ameliorate neurological impairments in rats afflicted with cerebral IR injury. Beyond its neurological benefits, NA demonstrates its potential by rectifying metabolic perturbations across diverse pathways, particularly those pertinent to unsaturated fatty acid metabolism. Additionally, NA emerges as a modulator of gut microbiota composition, notably by selectively enhancing vital genera like Lactobacillus. Conclusion These comprehensive findings highlight the potential of incorporating NA as a functional component in dietary interventions aimed at targeting cerebral IR injury. Nervonic acid demonstrates the capability to mitigate neurological impairments in rats afflicted with cerebral ischemia‐reperfusion injury. Its neuroprotective effects are proposed to involve the correction of the abnormal composition of gut microbiota and the resolution of metabolic perturbations across diverse pathways, specifically those intricately linked to unsaturated fatty acid metabolism, thereby contributing to its overall efficacy. Additionally, the study identifies 12 potential biomarkers in fecal samples that exhibit a high correlation with the regulation of gut microbiota in response to nervonic acid treatment, underscoring a specific and measurable impact on the gut microbial community.