Ischemic stroke has been demonstrated to cause an imbalance of gut microbiota. However, it remains unclear how the change of gut microbiota-mediated bile acids (BAs) metabolites. Here, we observed a decrease in gut microbiota-mediated BA, especially ursodeoxycholic acid (UDCA), in the serum of stroke patients as well as in the intestine, serum and brain of stroke mice. Restoration of UDCA could decrease the area of infarction and improve the neurological function and cognitive function in mice in association with inhibition of NLRP3-ralated pro-inflammatory cytokines through TGR5/PKA pathway. Furthermore, knocking out TGR5 and inhibiting PKA activity reduce the protective effect of UDCA. Taken together, our results suggest that microbiota-mediated UDCA play an important role in alleviating inflammatory responses and might be a promising therapeutic target in ischemic stroke.

缺血性中风已被证明会导致肠道微生物群失衡。然而，目前尚不清楚肠道微生物群介导的胆汁酸（BA）代谢物的变化如何。在这里，我们观察到中风患者血清以及中风小鼠的肠道、血清和大脑中肠道微生物群介导的 BA，尤其是熊去氧胆酸 (UDCA) 减少。恢复 UDCA 可以减少梗死面积，改善小鼠的神经功能和认知功能，与通过 TGR5/PKA 途径抑制 NLRP3 相关的促炎细胞因子有关。此外，敲除 TGR5 和抑制 PKA 活性会降低 UDCA 的保护作用。综上所述，我们的结果表明微生物介导的 UDCA 在减轻炎症反应中发挥着重要作用，并且可能是缺血性中风的一个有前途的治疗靶点。