Recent evidence demonstrated that functional bacteria were involved in the regulation of Parkinson’s disease (PD). However, the mechanism of probiotics in improving PD was unclear. Here the antioxidant effect and the mechanism of probiotics Pediococcus pentosaceus (PP) on PD were studied by regulating the gut–brain axis. In this study, male C57BL/6J mice were injected with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intraperitoneally to establish a PD model and were then treated with PP for 4 weeks. Subsequently, a series of neurobehavioral tests to evaluate the motor function of the mice was performed. Additionally, degeneration of dopaminergic neurons, accumulation of α-synuclein, the production of an oxidative stress response, and the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) pathway-related proteins were evaluated. Moreover, the gut microbial composition and the level of metabolite γ-aminobutyric acid (GABA) were assessed. The results showed that PP treatment could improve MPTP-induced motor deficits, the degeneration of dopaminergic neurons, and the accumulation of α-synuclein. Moreover, PP treatment significantly increased the levels of SOD1, Gpx1, and Nrf2, while it decreased the levels of Keap1 in the brain of MPTP-induced mice. Notably, PP treatment improved the gut microbial dysbiosis and increased the level of GABA in MPTP-induced mice. These findings indicated that PP might represent a promising candidate, due to the metabolite of GABA, that could be used for the treatment of PD.

The fungal microbiota may be involved in the regulation of cognition and behavior, while the role of probiotic fungi against cognitive impairment is unclear. Here, we explored the idea that probiotic Saccharomyces boulardii could participate in the regulation of microglia-induced neuroinflammation in Alzheimer's disease (AD) model mice. Cognitive deficits, deposits of amyloidβ (Aβ) and phosphorylation of tau, synaptic plasticity, microglia activation, and neuroinflammatory reactions were observed. The expression levels of Toll-like receptors (TLRs) pathway-related proteins were detected. Meanwhile, intestinal barrier integrity and fungal microbiota composition were evaluated. Our results showed fungal microbiota dysbiosis in APP/PS1 mice, which might result in the neuroinflammation of AD. The increased levels of interleukin (IL)-6, IL-1β, and cluster of differentiation 11b (CD11b) were observed in APP/PS1 mice, which were associated with activation of microglia, indicative of a broader recognition of neuroinflammation mediated by fungal microbiota compared to hitherto appreciated. Probiotic S. boulardii treatment improved dysbiosis, alleviated the neuroinflammation as well as synaptic injury, and ultimately improved cognitive impairment. Moreover, S. boulardii therapy could inhibit microglia activation and the TLRs pathway, which were reversed by antifungal treatment. These findings revealed that S. boulardii actively participated in regulating the TLRs pathway to inhibit the neuroinflammation via the gut− brain axis.

The mechanisms of coffee against Parkinson disease (PD) remained incompletely elucidated. Numerous studies suggested that gut microbiota played a crucial role in the pathogenesis of PD. Here, we explored the further mechanisms of coffee against PD via regulating gut microbiota. C57BL/6 mice were intraperitoneally injected with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to induce a PD mouse model, then treated with coffee for 4 consecutive weeks. Behavioral tests consisting of the pole test and beam-walking test were conducted to evaluate the motor function of mice. The levels of tyrosine hydroxylase (TH) and α-synuclein (α-syn) were assessed for dopaminergic neuronal loss. The levels of occludin, glial fibrillary acidic protein (GFAP), Bcl-2, Bax, cleaved caspase-3, and cytochrome c (Cyt c) were detected. Moreover, microbial components were measured by 16s rRNA sequencing. Our results showed that coffee significantly improved the motor deficits and TH neuron loss, and reduced the level of α-syn in the MPTP-induced mice. Moreover, coffee increased the level of BBB tight junction protein occludin and reduced the level of astrocyte activation marker GFAP in the MPTP-induced mice. Furthermore, coffee significantly decreased the levels of proapoptotic proteins, including Bax, cleaved caspase-3, and cytochrome c, while it increased the level of antiapoptotic protein Bcl-2, consequently preventing MPTP-induced apoptotic cascade. Moreover, coffee improved MPTP-induced gut microbiota dysbiosis. These findings suggested that the neuroprotective effects of coffee on PD were involved in the regulation of gut microbiota, which might provide a novel option to elucidate the effects of coffee on PD.

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