Probiotic Pediococcus pentosaceus ameliorates MPTP-induced oxidative stress via regulating the gut microbiota–gut–brain axis

Abstract

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.

Buty and the beast: the complex role of butyrate in Parkinson’s disease

“…This can have a complimentary effect in that the butyrate levels are restored in addition to suppressing the outgrowth of other non-beneficial and sometimes inflammatory bacteria. After the administration of probiotics, prebiotic fibers (including oligosaccharides), or a high-fiber diet several studies investigated the gut microbial changes and the consequent effects on PD symptoms ( Perez-Pardo et al, 2017 ; 2018 ; Srivastav et al, 2019 ; Ghyselinck et al, 2021 ; Li T. et al, 2022 ; Pan et al, 2022 ) (Studies are summarized in Table 2 ).…”

“…In animal models of PD, the supplementation of various probiotics, all belonging to the phylum Bacillota, resulted in gut microbiota composition alterations and is associated with increased levels of fecal butyrate ( Srivastav et al, 2019 ; Li T. et al, 2022 ; Pan et al, 2022 ). When investigating the neuroprotective effects of this supplementation in the brain, it was found that DA neurons were protected from cell death, glial cell hyperactivation was suppressed, and neuroinflammation was reduced ( Srivastav et al, 2019 ; Li T. et al, 2022 ).…”

“…One study, however, attributed the motor symptom improvement to the bacterial metabolite γ-aminobutyric acid (GABA), as increased GABA levels were observed in the brains of treated mice compared to the PD model ( Pan et al, 2022 ). This metabolite is predominantly produced by bacteria belonging to the Bacteroides genus, of which the relative abundance is found to be increased in some studies or decreased in others with regard to PD microbiome ( Nuzum et al, 2020 ; Romano et al, 2021 ).…”

Selection of Fermentation Supernatant from Probiotic Strains Exhibiting Intestinal Epithelial Barrier Protective Ability and Evaluation of Their Effects on Colitis Mouse and Weaned Piglet Models

“…In comparison to live bacteria, postbiotics have more versatile characteristics, including a clear chemical structure, safe dosage parameters, and a lack of the potential risks associated with live bacteria. As a result, postbiotics have emerged as a promising strategy for promoting healthy food and treating diseases [ 13 , 14 , 15 ]. The cell-free supernatant (CFS) produced by bacterial fermentation contains postbiotics secreted by the indicated probiotics, which have been shown to have protective effects on the intestine similar to those of live bacteria, suggesting that their active substances come from soluble molecules in the supernatant that can regulate the secretion of inflammatory factors or activate related immune cells [ 16 ].…”

Bacillus amyloliquifaciens-Supplemented Camel Milk Suppresses Neuroinflammation of Autoimmune Encephalomyelitis in a Mouse Model by Regulating Inflammatory Markers

“…Moreover, further evidence showed the level of GABA was reduced in neuropsychiatric diseases [ 29 , 30 ]. Interestingly, intestinal microbiota, such as Lactobacillus SPP and Bifidobacterium , can produce GABA mediators [ 31 ]. It was also evidenced that treatment with probiotics for 4 weeks significantly improved the gastrointestinal symptoms in patients with Parkinson’s disease through the secretion of GABA factors.…”