Lactiplantibacillus plantarum SG5 inhibits neuroinflammation in MPTP-induced PD mice through GLP-1/PGC-1α pathway

Mounting evidence suggests that alterations in gut microbial composition play an active role in the pathogenesis of Parkinson's disease (PD). Probiotics are believed to modulate gut microbiota, potentially influencing PD development through the microbiota-gut-brain axis. However, the potential beneficial effects of Lactiplantibacillus plantarum SG5 (formerly known as Lactobacillus plantarum, abbreviated as L. plantarum) on PD and its underlying mechanisms remain unclear. In this study, we employed immunofluorescence, Western blotting, ELISA, and 16S rRNA gene sequencing to investigate the neuroprotective effects of L. plantarum SG5 against neuroinflammation in an MPTP-induced PD model and to explore the underlying mechanisms. Our results demonstrated that L. plantarum SG5 ameliorated MPTP-induced motor deficits, dopaminergic neuron loss, and elevated α-synuclein protein levels. Furthermore, SG5 inhibited MPTP-triggered overactivation of microglia and astrocytes in the substantia nigra (SN), attenuated disruption of both blood-brain and intestinal barriers, and suppressed the release of inflammatory factors in the colon and SN. Notably, SG5 modulated the composition and structure of the gut microbiota in mice. The MPTP-induced decrease in colonic GLP-1 secretion was reversed by SG5 treatment, accompanied by increased expression of GLP-1R and PGC-1α in the SN. Importantly, the GLP-1R antagonist Exendin 9-39 and PGC-1α inhibitor SR18292 attenuated the protective effects of SG5 in PD mice. In conclusion, we demonstrate a neuroprotective role of L. plantarum SG5 in the MPTP-induced PD mouse model, which likely involves modulation of the gut microbiota and, significantly, the GLP-1/PGC-1α signaling pathway.