Lactobacillus plantarum CCFM405 against Rotenone-Induced Parkinson’s Disease Mice via Regulating Gut Microbiota and Branched-Chain Amino Acids Biosynthesis

Abstract

Recent studies have demonstrated that disturbances in the gut microbiota and microbiota -derived metabolites contribute to the pathogenesis of Parkinson's disease (PD), suggesting that probiotic treatments that restore them may delay disease progression. This study aimed to examine the attenuating efficacy of <i>L. plantarum</i> CCFM405 and the potential mechanisms in mice with rotenone-induced PD. Our results indicate that <i>L. plantarum</i> CCFM405 ameliorated rotenone-induced motor deficits and constipation, decreased dopaminergic neuronal death, reduced intestinal inflammation and neuroinflammation, and raised dopamine levels, 5-HT, and associated metabolites in the striatal region of the brain in mice with PD. Sequencing of 16S rRNA from fecal microbiota revealed that <i>L. plantarum</i> CCFM405 normalized the gut bacterial composition in mice with PD, as evidenced by the increased relative abundance of the following genus, <i>Bifidobacterium</i>, <i>Turicibacter</i>, and <i>Faecalibaculum</i>, and decreased relative abundance of <i>Alistipes</i>, <i>Bilophila</i>, <i>Akkermansia</i>, and <i>Escherichia-Shigella</i>. The PICRUSt-predicted gut microbiota function revealed that <i>L. plantarum</i> CCFM405 enhanced the biosynthesis of amino acid pathways, particularly valine, leucine, and isoleucine (branched-chain amino acids, BCAAs). A non-metabolomic analysis of the serum and feces showed that <i>L. plantarum</i> CCFM405 markedly increased the levels of BCAAs. Pathway enrichment analysis based on the KEGG database further suggested that <i>L. plantarum</i> CCFM405 supplementation can promote BCAAs biosynthesis. Collectively, <i>L. plantarum</i> CCFM405 can help to prevent rotenone-induced PD by modulating the gut microbiota-metabolite axis. BCAAs may play a dominant role in <i>L. plantarum</i> CCFM405-associated neuroprotection in PD mice. This probiotic could be utilized as a potential food supplement in the management of PD.