Parkinson’s disease (PD) is a common degenerative disease of the central nervous system. Although some drugs can alleviate the progress of PD, their long-term use will lead to complications, so it is still necessary to find new drugs to delay or cure PD effectively. In view of the difficulty in developing new drugs, it is imperative to discover new functions of existing compounds that could be used to treat PD. In this study, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was used to induce PD symptoms in a mouse model. Subsequently, these mice were treated with the antibiotic ceftriaxone. Ceftriaxone alleviated the behavioural and neuropathological changes induced by MPTP, downregulated the expression of glial fibrillary acidic protein (GFAP) and ionised calcium-binding adapter molecule 1 (Iba1) as markers of astroglia and microglia, respectively, and reduced the expression of neuroinflammation-related Toll-like receptor 4 (TLR4), myeloid differentiation primary response 88 (MyD88), and phosphorylated nuclear factor kappa-B (p-NF-κB)/NF-κB in the brain of PD mice. In addition, ceftriaxone reduced the abundance of pathogenic bacteria of the genus Proteus and increased the abundance of probiotic Akkermansia. Finally, ceftriaxone treatment increased the expression of the tight junction proteins zona occludens-1(ZO-1) and occludin in the colon, decreased the expression of the inflammation-related proteins TLR4, MyD88, and NF-κB in the colon, and decreased the serum concentration of the proinflammatory cytokines interleukin-1β (IL-1β), IL-6, and tumour necrosis factor-α (TNF-α). These results indicate that ceftriaxone had a neuroprotective effect on MPTP-induced PD mice, and its neuroprotective effect could be through regulating inflammation and intestinal microbiota. While we showed that ceftriaxone exerts a neuroprotective effect in an MPTP-induced PD mouse model, our findings are limited to the short-term effects of ceftriaxone. Additional work using transgenic mice is required to determine the long-term effects of ceftriaxone. In addition, the dose and frequency of ceftriaxone use should be evaluated.

Parkinson’s disease (PD) is a neurodegenerative disease (NDD) with high and ongoing morbidity, bringing heavy burdens to PD patients seriously. Finding neurotrophic drugs still remains vital due to the limited drug spectrum available currently. Substantial evidence suggests that glucagon-like peptide 1 (GLP-1) exerts neuroprotection on PD, yet the short-lived biological activity markedly hindered its application. Herein, we investigated the neurotrophic role of the next-generation probiotic strain L. lactis MG1363-pMG36e-GLP-1 in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mice and elucidated the mechanisms. Our data suggested that L. lactis MG1363-pMG36e-GLP-1 markedly enhanced motor deficits induced by MPTP via rescuing dopaminergic (DAergic) neurodegeneration in substantia nigra (SN). We found that L. lactis MG1363-pMG36e-GLP-1 exerts neurotrophic effects via activating the Keap1/Nrf2/GPX4 signalling pathway to down-regulate ACSL4 and up-regulate FSP1 to suppress ferroptosis. Additionally, the decreased oxidative stress levels via suppressing generations of ROS and MDA supported our findings. Lastly, we identified that the L. lactis MG1363-pMG36e-GLP-1 administration reversed dysbiosis in PD mice by increasing Akkermansia, Oscillospira, and Sutterella at the genus level. These results indicated that the neurotrophic effects of the next-generation probiotics L. lactis MG1363-pMG36e-GLP-1 against MPTP-induced Parkinsonism are mediated by modulating oxidative stress, inhibiting ferroptosis, and redressing dysbiosis.

Population aging is a prominent global problem in today’s society. However, there are currently no good methods to treat or prevent aging, so anti-aging research has crucial implications. In this research, we screened bacteria from centenarians, and finally selected four probiotics (Lactobacillus fermentum SX-0718, L. casei SX-1107, Bifidobacterium longum SX-1326, and B. animalis SX-0582) to form a probiotic combination. By using the senescence accelerated mouse prone 8 (SAMP8) model, the anti-aging effects of the probiotic combination were evaluated by using behavioural testing, neuroinflammation, intestinal inflammation, and intestinal microbiota. The results showed that probiotic combination improved the impaired spatial memory, motor dysfunction, and decreased exploratory behavior in aging mice. The probiotic combination inhibited Toll-like receptor 4 (TLR4)/nuclear factor kappa B (NFκB)-induced neuroinflammation and up-regulated the expression of Sirt 1 to protect hippocampal neurons. At the same time, the probiotic combination regulated the intestinal microbiota, reduced the relative abundance of Alistipes and Prevotella in SAMP8 mice, inhibited TLR4/NFκB-induced intestinal inflammation, and increased the expression of intestinal permeability related proteins zonula occludens-1 (ZO-1) and Occuldin. The anti-aging effects of the probiotic combination may be through the regulating intestinal microbiota and inhibiting TLR4/NFκB-induced inflammation. This research provides the basis and technical support for the future production and application of the probiotic combination.

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