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 L. plantarum CCFM405 and the potential mechanisms in mice with rotenone-induced PD. Our results indicate that L. plantarum 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 L. plantarum CCFM405 normalized the gut bacterial composition in mice with PD, as evidenced by the increased relative abundance of the following genus, Bifidobacterium, Turicibacter, and Faecalibaculum, and decreased relative abundance of Alistipes, Bilophila, Akkermansia, and Escherichia-Shigella. The PICRUSt-predicted gut microbiota function revealed that L. plantarum 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 L. plantarum CCFM405 markedly increased the levels of BCAAs. Pathway enrichment analysis based on the KEGG database further suggested that L. plantarum CCFM405 supplementation can promote BCAAs biosynthesis. Collectively, L. plantarum CCFM405 can help to prevent rotenone-induced PD by modulating the gut microbiota–metabolite axis. BCAAs may play a dominant role in L. plantarum CCFM405-associated neuroprotection in PD mice. This probiotic could be utilized as a potential food supplement in the management of PD.

The interplay between gut microbiota and the brain-gut axis in Parkinson’s disease treatment

“…FMT: FMT, the process of transferring fecal matter from a healthy donor to a patient's gastrointestinal tract, aims to re-establish a balanced microbiome (25,29,34,35,44,45,(54)(55)(56)(57)(58)(59)(60)(61). Initially utilized for Clostridium difficile infections, FMT is now being explored as a viable treatment option for PD (34,35,45,54,57,60,61).…”

“…FMT: FMT, the process of transferring fecal matter from a healthy donor to a patient's gastrointestinal tract, aims to re-establish a balanced microbiome (25,29,34,35,44,45,(54)(55)(56)(57)(58)(59)(60)(61). Initially utilized for Clostridium difficile infections, FMT is now being explored as a viable treatment option for PD (34,35,45,54,57,60,61). By directly modifying the gut microbiota, FMT seeks to rectify the dysbiosis prevalent in PD patients, thereby possibly reducing systemic and neuroinflammation while providing neuroprotective advantages (25,29,34,35,44,45,(54)(55)(56)(57)(58)(59)(60)(61).…”

“…Initially utilized for Clostridium difficile infections, FMT is now being explored as a viable treatment option for PD (34,35,45,54,57,60,61). By directly modifying the gut microbiota, FMT seeks to rectify the dysbiosis prevalent in PD patients, thereby possibly reducing systemic and neuroinflammation while providing neuroprotective advantages (25,29,34,35,44,45,(54)(55)(56)(57)(58)(59)(60)(61). Despite its potential, the efficacy and safety of FMT for PD treatment require more extensive clinical investigation (25,29,34,35,44,45,(54)(55)(56)(57)(58)(59)(60)(61).…”

Pesticides in Foods: Towards Bioremediation Biocatalysts?

“…In addition, they even promote plant growth and fulfill the various roles of agrochemicals [41]. At the other end of the pesticide contamination chain, they can exhibit a protective effect on animals with pesticide-induced diseases [42,43]. In between, they can decrease intestinal absorption of pesticides by adsorbing the compounds on their surface [44,45], and of course, they can participate in pesticide degradation [23].…”

Emerging therapeutic role of gut microbial extracellular vesicles in neurological disorders

“…Lactobacillus plantarum is an abundant family of probiotics, and multiple subtypes are neuroprotective in PD. Lactobacillus plantarum CCFM405 alleviates rotenone-induced PD mice via regulating gut microbiota and branched-chain amino acids biosynthesis ( Chu et al, 2023 ). Lactobacillus plantarum DP189 reduces α-synuclein aggravation in MPTP-induced PD in mice via regulating oxidative damage, inflammation, and gut microbiota disorder ( Wang et al, 2022 ).…”