Lactobacillus taiwanensis BCRC17755 alleviates motor dysfunction and dopaminergic neuronal loss in mouse models of Parkinson's disease.

Abstract

Parkinson's disease (PD) is a complex progressive neurodegenerative disease characterized by both motor and nonmotor symptoms such as constipation and dyspepsia. Recently, growing evidence has suggested that a specific gut microbiome is associated with the pathophysiology of PD through the microbiota-gut-brain axis. We previously discovered that Proteus mirabilis induced motor impairment and brain dopaminergic neurodegeneration in normal mice. In this context, exploring beneficial microbe would be reasonable strategy to treat PD fundamentally. With that the current study aimed to evaluate whether Lactobacillus taiwanensis BCRC17755 (BCRC17755) could ameliorate PD pathologies induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and P. mirabilis in mice. To demonstrate this, we measured motor function by performing pole test and the rotarod test and conducted histological analysis to assess the changes of factors in both brain and the gut. As a result, BCRC17755 decreased faecal abundance of P. mirabilis, which was higher in both the MPTP and P. mirabilis-treated mice. Additionally, BCRC17755 improved the motor deficits and alleviated damage to nigrostriatal dopaminergic neurons observed in both MPTP and P. mirabilis-induced PD mice. Furthermore, BCRC17755 mitigated microglial hyperactivation triggered by MPTP and P. mirabilis in the substantia nigra pars compacta and striatum of mice. Similarly, the release of inflammatory cytokines, including interleukin-1 beta and tumor necrosis factor alpha, was suppressed following the administration of BCRC17755 in the colon. Taken together, all the results suggest that BCRC17755 is a beneficial microbe for the treatment of PD by inhibiting the P. mirabilis growth.