Probiotic Clostridium butyricum ameliorated motor deficits in a mouse model of Parkinson's disease via gut microbiota-GLP-1 pathway.

A connection between gut microbiota and Parkinson's disease (PD) indicates that dysbiosis of the gut microbiota might represent a risk factor for PD. Microbiota-targeted interventions, including probiotic Clostridium butyricum (Cb), have been recently shown to have favorable effects in PD by regulating microbiota-gut-brain axis. However, the potential beneficial roles and its mechanisms of Cb on PD were still unknown. Male C57BL/6 mice were subjected to a PD model-induced by 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) and were treated intragastrically with Cb for 4 weeks. The motor functions were assessed by a series of behavioral tests including pole test, beam walking teat, forced swimming test and open field test. The dopaminergic neuron loss, synaptic plasticity and microglia activation, as well as the levels of colonic glucagon-like peptide-1 (GLP-1), colonic G protein-coupled receptors GPR41/43 and cerebral GLP-1 receptors were assessed. Gut microbial composition was assessed by 16S rRNA sequencing analysis. Our results showed that oral administration of Cb could improve motor deficits, dopaminergic neuron loss, synaptic dysfunction and microglia activation in the MPTP-induced mice. Meanwhile, Cb treatment could reverse the dysbiosis of gut microbiota and the decreased levels of colonic GLP-1, colonic GPR41/43 and cerebral GLP-1 receptor in the MPTP-induced mice. These findings indicated that the neuroprotective mechanism of Cb on PD might be related to the improvement of abnormal gut microbiota-gut-brain axis.

Anti-neuroinflammatory Effect of Short-Chain Fatty Acid Acetate against Alzheimer's Disease via Upregulating GPR41 and Inhibiting ERK/JNK/NF-κB.

Alzheimer's disease (AD) is a high-incidence neurodegenerative disease in the elderly. Acetate (Ace) is a short-chain fatty acid (SCFA) with neuroprotective activity. The purpose of this study was to investigate the effects and its possible mechanisms of SCFA Ace on AD. A male APP/PS1 transgenic mouse was given intragastric administration Ace for 4 weeks. Cognitive function and microglia activation in mice were assessed. Furthermore, Ace pretreated amyloid-ß (Aß)-induced BV2 microglia, and the levels of CD11b, COX-2, and G-protein-coupled receptor 41 (GPR41) and phosphorylation of ERK, JNK, and NF-κB p65 were determined. Our results revealed that Ace significantly attenuated the cognitive impairment and decreased the CD11b level in the APP/PS1 mice. Moreover, Ace inhibited the phosphorylation of NF-κB p65, ERK, and JNK and decreased the levels of COX-2 and interleukin 1ß in the Aß-stimulated BV2 microglia. Finally, Ace increased the GPR41 level in the Aß-stimulated BV2 cells. The finding indicated that Ace exerted antineuroinflammatory effects via the upregulation of GPR41 and suppression of the ERK/JNK/NF-κB pathway, which might provide an alternative therapy strategy of AD.