Gut microbiota regulation by Lactiplantibacillus plantarum SG5 enhances mitochondrial function in Parkinson's disease mice via the GLP-1/PGC-1α pathway.

Motor dysfunction constitutes a prominent characteristic of Parkinson's disease (PD), a neurodegenerative disorder associated with compromised mitochondrial activity, perturbed gut microbial composition, and neuronal loss. In this study, we examined the regulatory mechanisms of Lactiplantibacillus plantarum SG5 (L. plantarum SG5) on mitochondrial function in PD mouse models, with a particular emphasis on its interaction with the GLP-1/PGC-1α pathway. Findings revealed that MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, MPTP) induced (male 6-8 weeks C57BL/6 mice) motor impairments and damage to dopaminergic (DA) neurons in PD mice, resulting in mitochondrial dysfunction, decreased mitochondrial biogenesis, disrupted dynamics, and autophagy, while promoting fission and apoptosis. Additionally, MPTP modified gut microbial diversity and community structure. Nevertheless, supplementation with SG5 alleviated motor deficits and DA neurons damage in PD mice, enhancing mitochondrial quality by elevating PGC-1α expression and restoring biogenesis, dynamics, and autophagy levels. Mechanistic investigations demonstrated that SG5 increased colonic GLP-1 expression, suggesting that GLP-1 might regulate mitochondrial function via the GLP-1R-mediated PGC-1α. Furthermore, SG5 counteracted MPTP-induced gut dysbiosis. Notably, both GLP-1R antagonists and PGC-1α inhibitors attenuated the protective effects of SG5 in PD mice. In conclusion, L. plantarum SG5 may enhance mitochondrial function in the substantia nigra (SN) of PD mice through the GLP-1/PGC-1α pathway, potentially delaying neurodegeneration. Its mechanism is closely related to the regulation of the gut microenvironment and GLP-1 levels, presenting novel microbiota-based therapeutic targets for PD.