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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\u2013metabolite 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.<\/jats:p>","DOI":"10.3390\/nu15071737","type":"journal-article","created":{"date-parts":[[2023,4,3]],"date-time":"2023-04-03T01:37:05Z","timestamp":1680485825000},"page":"1737","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":69,"title":["Lactobacillus plantarum CCFM405 against Rotenone-Induced Parkinson\u2019s Disease Mice via Regulating Gut Microbiota and Branched-Chain Amino Acids Biosynthesis"],"prefix":"10.3390","volume":"15","author":[{"given":"Chuanqi","family":"Chu","sequence":"first","affiliation":[{"name":"State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China"},{"name":"School of Food Science and Technology, Jiangnan University, Wuxi 214122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3191-3123","authenticated-orcid":false,"given":"Leilei","family":"Yu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China"},{"name":"School of Food Science and Technology, Jiangnan University, Wuxi 214122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9688-0393","authenticated-orcid":false,"given":"Yiwen","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Food Science and Technology, The University of Georgia, Athens, GA 30602, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2720-0347","authenticated-orcid":false,"given":"Hang","family":"Guo","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China"},{"name":"School of Food Science and Technology, Jiangnan University, Wuxi 214122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0605-2675","authenticated-orcid":false,"given":"Qixiao","family":"Zhai","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China"},{"name":"School of Food Science and Technology, Jiangnan University, Wuxi 214122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China"},{"name":"School of Food Science and Technology, Jiangnan University, Wuxi 214122, China"},{"name":"National Engineering Research Center for Functional Food, Jiangnan University, Wuxi 214122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengwei","family":"Tian","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China"},{"name":"School of Food Science and Technology, Jiangnan University, Wuxi 214122, China"},{"name":"National Engineering Research Center for Functional Food, Jiangnan University, Wuxi 214122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1016\/S1474-4422(17)30299-5","article-title":"Global, regional, and national burden of neurological disorders during 1990\u20132015: A systematic analysis for the Global Burden of Disease Study 2015","volume":"16","author":"Feigin","year":"2017","journal-title":"Lancet Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1001\/jamaneurol.2017.3299","article-title":"The Parkinson Pandemic\u2014A Call to Action","volume":"75","author":"Dorsey","year":"2018","journal-title":"JAMA Neurol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1038\/nrn983","article-title":"Pathogenesis of Parkinson\u2019s disease: Dopamine, vesicles and alpha-synuclein","volume":"3","author":"Lotharius","year":"2002","journal-title":"Nat. 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