<i>Prevotella Histicola</i> Inhibits Neuroinflammation-Induced Activation of the Toll-Like Receptor 4 Pathway by Promoting the Release of Interleukin 10 from FoxP3+ Treg Cells

Background Accumulating evidence indicates that intestinal microbiota not only influence development and behavior but also play important roles in the pathogenesis of neurodegenerative diseases. However, the relationships between gut bacteria and diseases of the nervous system remain to be fully explored. Microglial activation has been identified as an important factor affecting the progression of many degenerative diseases. Therefore, we aimed to investigate the effects of Prevotella histicola on neuroinflammation and associated mechanisms in an animal model of dopaminergic neuron death caused by microglia activation. Methods We used the Toll-like receptor 4 (TLR4) agonist lipopolysaccharide (LPS) to establish an animal model of dopaminergic neuron death induced by microglia activation. LPS was injected into the mouse substantia nigra, followed by gavage with P. histicola . Results P. histicola inhibited LPS-induced microglia activation by increasing the proportion of peripheral regulatory T cells (Treg), thereby increasing the secretion of interleukin (IL)-10, reducing dopaminergic neuron damage, stimulating activation of anti-inflammatory M2 type microglia, and improving exercise capacity. Interestingly, P. histicola treatment suppressed the expression of SUMO-specific protease 3 (SENP3), which plays an important role in LPS-stimulated inflammatory TLR4 signaling. P. histicola treatment also downregulated inflammatory factors including IL-1, IL-6, IL-12, and tumor necrosis factor-alpha (TNFα). Conclusion These results suggest that P. histicola inhibits the TLR4 inflammatory signaling pathway and release of inflammatory factors by regulating the release of IL-10 from FoxP3 + Treg cells in the spleen. Our findings may provide insight into a new therapeutic avenue for attenuating the progression of degenerative diseases involving microglial activation.