Rhubarb with Different Cooking Methods Restored the Gut Microbiota Dysbiosis and SCFAs in Ischemic Stroke Mice

Ischemic stroke is a significant public health problem worldwide. Growing evidence has shown gut microbiota served a vital function in ischemic stroke. Rhubarb, always used after processing, is a promising therapy for ischemic stroke. However, the possible mechanism of rhubarb with different cooking methods has remained unclear. Herein, the constitutes of steaming rhubarb (SP), raw rhubarb (RP), and nine steaming nine sun-drying rhubarb (NSP) were identified via LC-QTOF-MS. The middle cerebral artery occlusion (MCAO) mice model was constructed. Infarction area, neurological score, Nissl staining, IBA-1 immunofluorescence, and ELISA were performed to confirm the neuroprotective effect of SP, RP, and NSP. The gut microbiota in fetal was studied via 16sRNA sequencing, and the level of short-chain fatty acids (SCFAs) in brain and gut were measured via GC-MS. The function of microbiota signature was identified through PICRUSt2; the possible mechanism was studied. SP, RP, and NSP alleviated the neurological dysfunction, decreased the inflammation, suppressed dysbiosis of gut microbiota, restored SCFA-producing bacteria, and enhanced the SCFA level in MCAO mice. Moreover, the NSP and SP enriched the proportion of anti-inflammation and beneficial bacteria, deleted the proportion of pro-inflammation. It observed energy metabolism was involved in the possible mechanism of rhubarb; activities of COXI and Na⁺-K⁺-ATPase were increased in the brain of NSP and SP treatment mice. Furthermore, the expression of GLUT4 and PFK1 (the energy metabolism-related genes) was elevated in the brain after RP, NSP and SP administration. In this study, it provided proof for the treatment of ischemic stroke with rhubarb. Rhubarb restored the gut microbiota and regulated the expression of GLUT4 and PFK1 to alleviate ischemic stroke.