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.
Highlights
Parkinson’s disease (PD) is a common neurodegenerative disease, characterized by loss of dopaminergic neurons and intracellular accumulation of alpha-synuclein (α-syn) in the surviving neurons [1]
Gender Comparing responses to probiotics in relation to gender, we found a statistically significant difference between male and female PD patients in reactive oxygen species (ROS) production from peripheral blood mononuclear cells (PBMCs)
The effect of LR06 was more pronounced in samples from male vs. female donors (81 and 60% reduction compared to baseline levels, respectively; p < 0.05; Table 4)
Summary
Parkinson’s disease (PD) is a common neurodegenerative disease, characterized by loss of dopaminergic neurons and intracellular accumulation of alpha-synuclein (α-syn) in the surviving neurons [1]. Involvement of inflammatory mechanisms, with an imbalance between detrimental and protective immune functions [2], as well as neurotoxicity of reactive oxygen species (ROS) have been documented by several studies [3, 4]. Both neuroinflammation and ROS may favor α-syn aggregation which may in turn increase pro-inflammatory cytokines and oxidative stress, triggering a vicious circle [5]. 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 The present study focused on the assessment of in vitro effects of probiotic bacterial strains in PBMCs isolated from PD patients vs. healthy controls
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