Bacteroides coprocola Protects Dopaminergic Neurons in Rotenone-Induced Parkinson’s disease Mice Model by Modulating Gut Microbiota Dysbiosis and Inhibiting the NLRP3 Signaling Pathway

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Abstract Background: Parkinson’s disease (PD) is a prevalent neurodegenerative disease and its pathogenesis is still unclear. Emerging evidence supports the gut-origin hypothesis, highlighting gut microbiota dysbiosis as a contributing factor in PD pathogenesis. Alterations in gut microbial composition influence barrier integrity and systemic chronic inflammation via the microbiota-gut-brain axis. Bacteroides coprocola (B.coprocola) , a gut bacterium producing short-chain fatty acids (SCFAs), is significantly reduced in PD patients from our previous clinical study. This study investigates B.coprocola ’s potential in ameliorating PD pathology using a rotenone-induced PD mouse model. By evaluating its impact on gut microbiota balance, inflammation, and macrophage polarization, we aim to elucidate its therapeutic role and underlying mechanisms in PD progression. Methods: In this study, the rotenone-induced PD mouse model was established. After three weeks of rotenone administration, PD mice underwent continuous oral gavage with B.coprocola for an additional three weeks. Motor function was assessed using the Rota-Rod test, Pole test, and Beam walking test. Furthermore, 16S rRNA high-throughput sequencing and targeted SCFAs metabolomics were employed to analyze gut microbiota composition and SCFAs levels across groups. Additionally, flow cytometry, immunofluorescence, qPCR, and Western blot techniques were utilized to examine alterations in midbrain and intestinal structures, NLRP3 inflammasome pathway activation, and macrophage polarization. Results: B.coprocola treatment could alleviate PD-related motor deficits, neuroinflammation, gut microbiota dysbiosis, and BBB and intestinal barrier permeability in the rotenone-induced PD mouse model. Additionally, B.coprocola inhibits the NLRP3 signaling pathway by modulating gut microbiota dysbiosis and macrophage polarization, ultimately alleviating systemic chronic inflammation and PD-like pathological symptoms in rotenone-induced mice. Conclusions: The current findings suggest that B.coprocola can regulate gut microbiota dysbiosis in rotenone-induced PD mice and influence macrophage polarization, which is associated with the inhibition of the NLRP3 inflammasome signaling pathway.

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