Probiotics May Have Beneficial Effects in Parkinson's Disease: In vitro Evidence

Abstract

Background: Parkinson's disease (PD) is characterized by loss of dopaminergic neurons and intraneuronal accumulation of alpha-synuclein, both in the basal ganglia and in peripheral sites, such as the gut. Peripheral immune activation and reactive oxygen species (ROS) production are important pathogenetic features of PD. In this context, the present study focused on the assessment of in vitro effects of probiotic bacterial strains in PBMCs isolated from PD patients vs. healthy controls. Methods: 40 PD patients and 40 matched controls have been enrolled. Peripheral blood mononuclear cells (PBMCs) were isolated and co-cultured with a selection of probiotics microorganisms belonging to the lactobacillus and bifidobacterium genus. In vitro release of the major pro- (Tumor Necrosis Factor-alpha and Interleukin-17A and 6) and anti-inflammatory (Interleukin 4 and 10) cytokines by PBMCs, as well as the production of ROS was investigated. Furthermore, we assessed the ability of probiotics to influence membrane integrity, antagonize the growth of potential pathogen bacteria, such as Escherichia coli and Klebsiella pneumoniae and encode tyrosine decarboxylase genes (tdc). Results: All probiotic strains were able to inhibit inflammatory cytokines and ROS production in both patients and controls. The most striking results were obtained in PD subjects with L. salivarius LS01 and L. acidophilus which significantly reduced pro-inflammatory and increased the anti-inflammatory cytokines (p < 0.05). Furthermore, most strains determined restoration of membrane integrity and inhibition of E. coli and K. pneumoniae. Finally, we also showed that all the strains do not carry tdc gene, which is known to decrease levodopa bioavailability in PD patients under treatment. Conclusions: Probiotics exert promising in vitro results in decreasing pro-inflammatory cytokines, oxidative stress and potentially pathogenic bacterial overgrowth. In vivo longitudinal data are mandatory to support the use of bacteriotherapy in PD.

Keywords: Parkinson's disease (PD); cytokines; neuroinflammation; oxidative stress; probiotic.

Figure 1

Modulation of cytokine production by probiotic strains. For each probiotic strain the first column indicates the baseline values, while the second after probiotic administration. *p < 0.001; #p < 0.05 post vs. pre-exposure from PD-PBMCs.

Figure 2

Reduction of superoxide anion (${\text{O}}_2^{-}$) production. *p < 0.01 post vs. pre-exposure from PD-PBMCs. #p < 0.05 post vs. pre-exposure from PMA-exposed HD-PBMCs.

Figure 3

Correlation between ROS production and disease duration for probiotic LA02 (p = 0.002).