Effects of a four-strain probiotic on inflammatory markers in Parkinson's disease: a multicentre randomised controlled trial (the SymPD study)
Valentina Leta1, Gargi Mandal1, Pavlos Zinzalias2, Juliet Staunton2, Lucia Batzu1, Dhaval Trivedi2, Kristina Rosqvist3, Jonathan Timpka3, Trinette van Vliet3, Aleksandra Podlewska1, Miriam Parry2, Daniel van Wamelen1, Alexandra Rizos2, Guy Chung-Faye2, Per Odin3, Carmine Pariante1, Alessandra Borsini1, K Ray Chaudhuri4
1King's College London, 2King's College Hospital, 3Lund University, 4King's College Hospital, London, UK
Objective:
To evaluate the effects of a four-strain probiotic (Lacticaseibacillus rhamnosus, Enterococcus faecium, Lactobacillus acidophilus, Lactiplantibacillus plantarum) on plasma levels of inflammatory markers in patients with Parkinson’s disease (PD) and symptomatic constipation recruited to the SymPD trial.
Background:
Pro-inflammatory gut dysbiosis and involvement of the ‘gut-brain’ axis have been described in PD and may be modulated by probiotics use. Preliminary results from the SymPD trial suggest that this four-strain probiotic can enrich the gut microbiota with bacteria having anti-inflammatory properties, reduce ‘time to on’, and non-motor symptoms burden in patients with PD and constipation.
Design/Methods:
A multicentre, randomised, double-blind, placebo-controlled trial of 74 patients with PD and constipation (ROME IV criteria) who were randomised (1:1) to either a four-strain probiotic (n=38) or placebo (n=36). Exploratory outcomes included measuring changes in the plasma levels of inflammatory cytokines such as IFN-γ, TNF-α, IL-6, IL-8, and IL-10 using the Human ProInflammatory Panel 1 Kit from Meso Scale Discovery after 12 weeks of intervention. Within-group changes were tested using the Wilcoxon signed-rank test (p≤0.05 was considered significant).
Results:
Blood samples from 22 and 19 participants from the active and placebo groups, respectively, were analysed. Significant reductions in the plasma levels of IL-6 (from 1.01±0.49 to 0.81±0.45 pg/mL, p=0.028) and TNF-α (from 2.04±1.40 to 1.69±0.93 pg/mL, p=0.024) were observed in the active treatment group, while a significant increase in the plasma levels of TNF-α (from 1.37±0.42 to 1.69±0.63 pg/mL, p=0.005) was observed in the placebo group.
Conclusions:
This four-strain probiotic was effective in reducing plasma levels of specific pro-inflammatory cytokines. This anti-inflammatory effect could partly underpin the improvements in motor and non-motor symptoms, particularly in fatigue, in patients with PD and constipation as observed in the SymPD trial.