Parkinson’s Disease (PD) is characterized by a loss of dopaminergic neurons and intraneural accumulation of alpha-synuclein, including in the gut. Neuroinflammation and oxidation may favor alpha-syn aggregation which may in turn increase pro-inflammatory cytokines and oxidative stress, triggering a vicious circle.
PD patients furthermore often suffer from non-motor symptoms like constipation (in 70 to 80% of cases), psychiatric disorders (anxiety and depression, possibly linked to neuroinflammation) and infections leading to hospitalization.
Probiotical proposed an integrated approach by testing selected probiotic bacteria on Polymorphic Blood Mononuclear Cells (PBMCs) from 40 PD patients matched with 40 healthy donors, evaluating bacteriotherapy as a co-adjuvant to the PD treatment. In a recent study (Magistrelli et al., 2019), 6 strains were evaluated for 6 traits that could help people with PD.
- Anti-inflammatory activity
The strains were selected based on anti-inflammatory activity in PBMCs of healthy donors, which also proved anti-inflammatory in contact with the immune cells of PD patients. The most striking results were obtained with L. salivarius LS01 (significant increases in anti-inflammatory IL-4 and IL-10, significant decreases in pro-inflammatory IL-6, TNF-alpha and IL-17A, all with p<0.001) and L. acidophilus LA02 (idem, except IL-4 was increased with a p<0.05).
These selected strains may therefore represent a promising strategy to counteract the detrimental immune activation that takes place in PD.
- Anti-oxidant activity
PD patients had almost 3 times the level of supeoxide anion production and over 63 times the amount of reduced cytochrome C as healthy donors, showing a very high level of oxidative stress. L. salivarius LS01, L. plantarum LP01, L. acidophilus LA02, L. rhamnosus LR06 and B. lactis BS01 caused a robust decrease of O2–production from PD PBMCs (p<0.01 post vs. pre-exposure).
They could therefore also support the body keep in check reactive oxygen species.
- Protection of Membrane Integrity
Several scientific papers report increased intestinal permeability in PD patients which could participate to the process of neuroinflammation. A monolayer of Caco-2 cells (human colonic cells with well-differentiated tight junctions) was exposed to a stressor and to the probiotic strains, while permeability was evaluated by Trans Epithelial Electrical Resistance (TEER). All the strains were able to strongly and significantly restore membrane integrity, from 40% after the damage alone to up to 100 % after damage and exposure (81% with LS01, and up to 100% with LP01 and LR06).
This is an important result that has implications also with regards to the risk of translocation of pathogenic bacteria of bacterial components (eg. Lipopolysaccharides, LPS) to the bloodstream or even across the Blood Brain Barrier.
- Capacity of inhibition against the major PD patients’ infections
Chih-Min Su et al.recently showed that E. coliand Klebsiella pneumoniae are among the leading three bacteria causing comorbidities in PD patients, respectively chronic cystitis and pneumonia. The 6 probiotic strains were co-cultured with pathogenic strains of E. coli and K. pneumoniae and all showed inhibitory capacity, at higher level than acidic pH alone, therefore highlighting a specific antagonism. L. plantarum LP01 and L. rhamnosus LR06 showed the highest inhibition.
The selected probiotics could support decreasing the abundance of pathogens in the gut and possibly decrease the risk of the leading severe infections of PD patients.
- Non-interference with drug treatment
People with Parkinson are commonly treated with the drug levodopa, and recent studies reported that commensal bacteria within the genera Lactobacillus and Enterococcus can produce tyrosine decarboxylase (tdc), which metabolize levodopa in the gut, leading to decreased efficacy and need for higher dosages. The whole genomes of all 6 strains were controlled and compared to the protein sequence responsible for levodopa inactivation, allowing to confirm the absence of the gene thus adding to the safety profile and absence of potential microorganism-drug interaction
Most PD patients also suffer from constipation, which sometimes precedes the disease diagnostic by as much as 20 years. The strains B. animaliss ubsp. lactis BS01, L. plantarum LP01 and B. breve BR03 clinically demonstrated significant improvements of constipation symtpoms (increase in weekly number of bowel movements, improvement in feces consistency, ease of expulsion and sense of complete emptying, as well as decrease in pain and abdominal bloating) in adults with evacuation disorders (Del Piano et al., 2010) and in chronically constipated seniors (Del Piano et al., 2005).
These strains could therefore be natural co-adjuvants to support patients with their gastrointestinal comfort.
All in all, the anti-inflammatory and anti-oxidant properties and protection of the gut barrier function traits, together with the pathogens control and gastrointestinal comfort are of importance for patients living with Parkinson disease, but are also more broadly interesting in an objective of healthy aging.