摘要Increasing evidence indicates that a healthy diet plays a protective role against ischemic stroke injury.As an antioxidant food,grape powder(GP)has been shown to have a neuroprotective function after ischemic injury.In the current research,we aimed to determine whether regular GP feeding before brain damage plays a protective role against ischemic damage and its potential mechanism.Mice had GP in drinking water(DW)for 4 weeks.Then,fecal samples were collected for 16S rRNA analysis and metabolite profiling.Ischemic stroke was triggered using GP prefeed mice by middle cerebral artery occlusion(MCAo)to compare the stroke-induced infarction size to the DW group.The data showed that 4 weeks of GP pretreatment significantly decreased the ischemic infarct size.Meanwhile,GP treatment altered the gut microbiota by enriching the population of Lachnospiraceae and enhancing a gut metabolite called fiestin,which belongs to the flavonoid group.Mechanistically,we demonstrated that fiestin could inhibit LPS-induced proinflammatory macrophage polarization in vitro.We also showed that regular GP feed could decrease stroke-induced neuroinflammation in vivo.In conclusion,our study demonstrated that 4 weeks of GP feeding attenuates experimental ischemic stroke via the gut-brain-immune axis.