Electroacupuncture (EA) is commonly used to treat
cerebrovascular diseases. This study aimed to clarify the mechanisms of action of treatments of cerebral
ischemic stroke from the perspective of gut microecology. We used a mouse model and cell cultures to investigate the effects of EA on the intestinal microflora in mice models of
middle cerebral artery occlusion (MCAO) and the mechanisms underlying the
antioxidant activities of metabolites.
Fecal microbiota transplantation (FMT) was used to validate the roles of gut microbiota. Metabolomic analysis was performed to characterize the metabolic profile differences between the mice in the EA + MCAO and MCAO groups. Gavaging with feces relieved brain damage in mice that received EA (EA mice) more than in mice that did not (non-EA [NEA] mice). The gut microbial composition and metabolic profiles of the EA and NEA mice were different. In particular, the microbiota from the mice in the EA or EA-FMT groups generated more indole-3-propionic
acid (IPA) than the microbiota from the mice in the MCAO or NEA-FMT groups. We confirmed that IPA binds to specific
melatonin receptors (MTRs) in target cells and exerts
antioxidant effects by adding MTR inhibitors or knocking out the MTR1 gene in vivo and in the
oxygen and
glucose deprivation/reperfusion models of N2a cell experiments. EA can prevent
ischemic stroke by improving the composition of intestinal microbiota in MCAO mice. Moreover, this study reveals a new mechanism of intestinal flora regulation of
stroke that differs from
inflammation/immunity, namely gut microbiota regulates
stroke by affecting IPA levels.