Gut commensal Parabacteroides distasonis exerts neuroprotective effects in acute ischemic stroke with hyperuricemia via regulating gut microbiota-gut-brain axis

作者：Hongming Wei, Lu Zhan, Xinhuang Lv, Yan Lin, Jie Zheng, Wenwen Yang, Jiaming Liu, Jing Sun, Songfang Chen · 发表于：Journal of Translational Medicine · 年份：2024 · DOI：10.1186/s12967-024-05800-9 · 被引用次数：10 · 研究领域：Gut microbiota and health、Neuroinflammation and Neurodegeneration Mechanisms、Tryptophan and brain disorders

BACKGROUND: Hyperuricemia is considered as an independent risk factor for acute ischemic stroke (AIS), and some AIS patients are accompanied by an increase in serum uric acid. Recent studies have highlighted the important role of gut microbiota in both hyperuricemia and AIS, but there is little available data on the relationship between gut microbiota and the pathogenesis of AIS with hyperuricemia (HAS). METHODS: Here we profiled the gut microbiota composition in 63 HAS patients and 269 non-HAS patients through 16s rRNA sequencing. Male rat with hyperuricemia were subjected to middle cerebral artery occlusion (MCAO) to establish HAS model and were then treated with Parabacteroides distasonis. Subsequently, the neurological deficit, pathological damages and blood-brain barrier disruption were evaluated. Moreover, the levels of ROS, inflammatory cytokines, NF-𝜿B pathway related protein, and vascular density markers were determined. RESULTS: There were significant differences of gut microbiota composition between HAS patients and non-HAS patients, and a significant decrease in the abundance of Parabacteroides in HAS patients compared to non-HAS patients. Animal experiments showed that supplementation with P. distasonis increased beneficial commensal bacteria, significantly improved neurological deficits, pathological damages and BBB disruption, as well as reduced the level of serum uric acid in HAS rats. We further demonstrated that P. distasonis treatment decreased ROS level an...