Sea buckthorn polysaccharide ameliorates high-fat diet induced mice neuroinflammation and synaptic dysfunction via regulating gut dysbiosis

Currently, definitive treatment for neurodegenerative diseases without side effects has not been developed, therefore, exploring natural polysaccharides with neuroprotection to prevent the occurrences and progressions of cognitive dysfunctions has important significance. The purpose of this study was to investigate the effects of sea buckthorn polysaccharide (SBP) on high-fat diet (HFD) induced mice cognitive dysfunctions and attempted to explore its biological mechanisms. Behavior tests (Y-maze and Barnes maze) suggested that SBP effectively alleviated the HFD induced behavioral disorders, which was in accordance with the inhibition of neuroinflammation via suppressing the NF-κB pathway and amelioration of synaptic dysfunction via upregulating CREB/BDNF/TrkB pathway in mice brain. Furthermore, SBP alleviated the gut barrier impairment, inflammatory responses, and lipopolysaccharide invasion into blood circulation via regulating the gut microbiome structure, especially correcting the reduction of Ileibacterium and increase of Lactobacillus, Dubosiella, Olsenella, Helicobacter, and Ruminiclostridium_9 in HFD mice. Therefore, the reversal effects of SBP on gut dysbiosis might be the important reason for its positive effects on cognitive dysfunction induced by HFD in mice.