Parkinson’s disease (PD) is a progressing neurodegenerative disease affecting the elderly and the most prevalent movement disorder known. About 8.5 million people worldwide have the disorder representing about 1-2% of persons over 60 years of age. In 2019, PD caused 329 000 deaths. As the elderly population continuously increase the number of persons, suffering from PD, will also rise. Even though the disease has been discovered and studied for more than 200 years, its causes remain obscure except for the about 5 % familiar cases.
The classic neuropathological finding in PD consists of cytoplasmic aggregates of α-synuclein protein (α-syn) visualized as Lewy bodies in the neurons (Chandra et al. 2017). Gastrointestinal non-motor symptoms are common such as constipation, and can appear more than 10 years before the onset of motor symptoms and diagnosis of PD. This has led e.g. to a suggestion that the etiological agent for the development of PD could be an environmental toxin potentially produced by bacteria in the intestine (Braak et al. 2003). However, no such toxin has been identified that could cause PD.
One candidate has been the curli protein of curli Escherichia coli, which can cause α-syn aggregations in PD model animals in intestinal cells, vagus nerve and brain (Chen et al. 2016). However, the presence of this bacteria does not correlate with PD.
Another candidate could be bacteria causing a leaky gut, like the Proteus mirabilis strain isolated from mice that could induce α-syn aggregation and inflammation in the gut in PD model mice upon oral administration (Choi et al. 2018). Intestinal dysbiosis and inflammation are typical findings in PD patients, but it is not known at what stage in the development of PD these symptoms evolve.
In a recent study, we demonstrated that Desulfovibrio bacteria (DSV) are more prevalent and exist in a significantly higher number (amount correlating even to disease severity) in the feces of PD patients than healthy volunteers (Murros et al. 2021).
Similar results were obtained later in China (Nie et al. 2023). This indicates that DSV species are associated with PD and are possibly involved in the disease pathogenesis. We proposed a hypothesis stating that DSV bacteria, through the hydrogen sulfide and/or magnetite formation, induce the α-synuclein accumulation in the intestinal EEC cells spreading via the vagus nerve to human brain and ultimately resulting in PD.
Recently Murros (2022) elaborated on the cellular mechanisms how hydrogen sulfide and magnetite produced by DSV, and other bacteria could cause aggregation of α-synuclein. We further showed that DSV strains isolated from PD patients can strongly induce alpha-synuclein aggregation, but not DSV strains isolated from healthy when the live bacteria are fed to PD model Caenorhabditis elegans worms (Huynh et al. 2023). This suggests further and stronger than correlation that DSV strains isolated from PD patients may have a role in the initial stage leading to PD.
Our aims are to verify the molecular mechanism how the Desulfovibrio strains isolated from PD patients contribute to the development of PD (if they really do it) and how they differ from Desulfovibrio strains isolated from healthy that cannot to the same extent cause alphasynuclein aggregation. This can give us tools to develop a vaccine against the potentially PD causing Desulfovibrio strains and enable prevention of PD.
Another line of research is to find ways to decrease or eradicate Desulfovibrio bacteria of the PD type using foods, antibiotics, antibacterial strains and phages utilizing the knowledge and methods we developed in our previous research related to food microbiology, fermentation, probiotics and intestinal microbiology. We continue research in these subjects as it can provide benefit also to our PD projects.