Lycium ruthenicum Murray anthocyanin-driven neuroprotection modulates the gut microbiome and metabolome of MPTP-treated mice

Emerging evidence suggests that Parkinson's disease (PD) is strongly associated with altered gut microbiota. The present study investigated the prophylactic effects of anthocyanins (ACNs) from Lycium ruthenicum Murray on Parkinson's disease based on microbiomics and metabolomics. In this study, sixty-six adult male C57BL/6J mice were randomized into the control group, model group, positive drug (Madopar) group, and low-, medium- and high-dose ACN groups. Behavioral experiments were conducted and pathological indicators were determined. Fresh feces were collected for microbiomic analysis using 16S rRNA sequencing. Urine and serum were analyzed by the UPLC-MS method for untargeted metabolomics. The results demonstrated that ACNs ameliorated 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced motor deficits, dopamine neuron death, and glial cell activation, while 100 mg kg^-1 and 200 mg kg^-1 ACNs were more neuroprotective than 50 mg kg^-1. Mice with PD-like phenotypes have an altered gut microbiota composition, and ACNs may regulate this disorder by causing an increase in Firmicutes/Bacteroidota ratio and abundance of norank_f__Eubacterium_coprostanoligenes_group and a decrease in the abundance of norank_f__Muribaculaceae, Coriobacteriaceae_UCG-002 and Parvibacter. Furthermore, ACNs increased 14 urinary key metabolites such as DIMBOA-Glc and tauroursodeoxycholic acid, decreased N,N-dimethyllysine, and increased 12 serum key metabolites such as 1-methylguanine and 1-nitro-5-glutathionyl-6-hydroxy-5,6-dihydronaphthalene, and decreased lamivudine-monophosphate and 5-butyl-2- methylpyridine. The present study reveals that ACNs are protective against MPTP-induced PD in mice by modulating anti-inflammatory flora in the gut and endogenous metabolites in serum/urine, and the key mechanisms may be related to Coriobacteriaceae_UCG-002 and glycerophospholipid metabolic pathways. Our findings provide new insights into the pathogenesis and potential treatment of Parkinson's disease.