Chicoric acid (CA), a polyphenolic acid obtained from chicory and purple coneflower (Echinacea purpurea), has been regarded as nutraceutical to combat inflammation, virus and obesity. Parkinson’s Disease (PD) is a common neurodegenerative disorder, and microbiota-gut-brain axis might be the potential mechanism in the pathogenesis and development of PD. The results here demonstrated that oral pretreatments of CA significantly prevented the 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-indued motor dysfunctions and death of nigrostriatal dopaminergic neurons, along with the inhibition on glial hyperactivation and the increment in striatal neurotrophins. 16S rRNA sequence results showed that CA significantly reduced MPTP-induced microbial dysbiosis and partially restored the composition of gut microbiota to normal, including decreased phylum Bacteroidetes and genera Parabacteroide, as well as increased phylum Firmicutes, genera Lactobacillus and Riminiclostridium. Besides, CA promoted colonic epithelial integrity and restored normal SCFAs production. We also observed the proinflammatory cytokines such as TNF-α and IL-1β in brain and gut were reduced by CA, indicating that CA prevented neuroinflammation and gut inflammation, in which the suppression of TLR4/MyD88/NF-B signaling pathway might be the underlying molecular mechanism. These findings demonstrated that the CA had neuroprotective effects on MPTP-induced PD mice possibly via modulating gut microbiota and inhibiting inflammation throughout the brain-gut axis. CLICK TO REVIEW