Heat‐killed Lactobacillus murinus confers neuroprotection against dopamine neuronal loss by targeting NLRP3 inflammasome

Abstract The intestinal flora has become very active in studies related to Parkinson's disease (PD) in recent years. The microbe‐gut‐brain axis is closely related to the maintenance of brain homeostasis as well as PD pathogenesis. Alterations in gut bacteria can contribute to neuroinflammation and dopamine (DA) neurodegeneration. Lactobacillus murinus, a gram‐positive bacterium, is a commensal gut bacteria present in the mammalian gut and considered as a potential probiotic due to its beneficial effects, including anti‐inflammatory and antibacterial actions. In this study, the effects of live L. murinus and heat‐killed L. murinus on DA neuronal damage in rats and the underlying mechanisms were investigated. Data showed that heat‐killed L. murinus ameliorated 6‐hydroxydopamine‐induced motor dysfunctions and loss of substantia nigra DA neurons, while no protection was shown in live L. murinus treatment. At the same time, heat‐killed L. murinus reduced the activation of NLRP3 inflammasome in microglia and the secretion of pro‐inflammatory factors, thus inhibiting the development of neuroinflammation. Furthermore, heat‐killed L. murinus failed to display its original neuroprotective properties in NLRP3 inflammasome knockout mice. Together, heat‐killed L. murinus conferred neuroprotection against DA neuronal loss via the inhibition of microglial NLRP3 inflammasome activation. These findings provide a promising potential for future applications of L. murinus, and also beneficial strategy for PD treatment.