Background Parkinson’s Disease (PD) is a common neurodegenerative disease. No disease-modifying treatment is available and therapy is symptomatic. The histopathologic hallmark is the loss of dopaminergic neurons and accumulation of α-synuclein (α-syn) in surviving neurons, but the underlying pathophysiology is unclear. Inflammatory mechanisms seem to play a prominent role, with an imbalance of immune functions and neurotoxicity caused by reactive oxygen species (ROS). An involvement of peripheral adaptive immunity, with an imbalance in T cell subpopulations and in the expression of transcriptional factors in CD4+ T cells has also been reported in PD patients. Although clinical presentation is defined by the presence of motor symptoms, patients often also report non-motor symptoms, often before the onset of a clinically established disease. Etiopathogenesis of PD is unknown, but an initial aggregation of α-syn in the gut with subsequent propagation along the vagus nerve to the brain has been hypothesised. Interestingly, in an α-syn overexpressing murine model, the absence of gut microbiota prevented both microglia activation and motor impairment, thus pointing to a fundamental role of microbiota in the development of PD. Magistrelli et al. showed that in peripheral blood mononuclear cells of PD patients, probiotics modulate the in vitro production of cytokines toward an antiinflammatory profile and to reduce the production of ROS.
Methods This is a pilot randomised placebo-controlled clinical trial. At least 80 patients affected by PD will be recruited and randomly allocated to either the treatment or placebo group in a 1:1 ratio. General inclusion criteria will be onset of PD 2 to 5 years before trial and absence of autoimmune comorbidities or immunomodulating therapy. Our primary endpoint is the assessment of changes in extracellular cytokine levels (Interferon (IFN)-γ, Tumor Necrosis Factor (TNF)-α, Interleukin (IL)-4 and IL-10), and ROS production. Secondary outcomes include changes in lymphocytes subpopulations, transcriptional factors mRNA levels.
Discussion This study is designed to highlight the potential beneficial role of probiotics administration on peripheral immunity through modulation of gut microbiota. Explorative outcomes will be evaluated to assess variations in motor and non-motor symptoms and the possible correlation with probiotics administration.
Trial registration ClinicalTrials.gov ID: NCT05173701. Registered 08 November 2021, https://clinicaltrials.gov/show/NCT05173701