Scientists from California (USA) revealed the role of gut bacteria in the progress of Parkinson's disease. Antibiotic treatment of mice overexpressing α-Synuclein ameliorated pathophysiology in adult animals, conceivably provides a new approach to treating Parkinson's disease.
Parkinson's Disease (PD) is a severe neurodegenerative disorder leading to motor deficits (trembling, rigidity, slow movement), impairment in thinking and interference of emotional cognition. It belongs to the so-called synucleinopathis, which are characterized by an accumulation of aggregates of alpha-synuclein (α-Syn). In PD, α-Syn is believed to oligomerize in a stepwise process in neurons, forming insoluble aggregates. Interestingly, Dopaminergic neurons of the substantia nigra seem to be specifically sensitive towards these aggregates and are massively affected in their function. Up to now, there is no cure for PD, however, many medications aim at modulating dopamine homeostasis but those medications can carry severe side effects and also often lose effectiveness over time.
Although neurological disorders are clearly associated with the central nervous system (CNS), the impact of the peripheral nervous system (PNS) on the progress of such diseases gets emerging attention by scientists. Several observations and studies suggest a co-occurrence of gastrointestinal symptoms and the progress of PD, however, the direct link between gut microbiota and the progression of PD has never been addressed before.
Scientists from California uncovered the role of gut bacteria in the progress of PD. They looked at a mouse model of PD that overexpressed α-Syn and that shows progressive deficits in motor function as well as in gastrointestinal function. Non-sterile mice were compared with antibiotic-treated germ-free (GF) littermates and several tests, investigating motor function and gut motility, revealed that GF mice performed much better. The colonization of the gut with microbiota was required for motor deficits, microglia activation, and α-Syn pathology, but just the oral administration of specific microbial metabolites, short-chain fatty acids (SCFAs), to germ-free mice was sufficient to promote neuroinflammation and motor deficits, mimicking PD. Moreover, microbiota derived from PD patients promoted increased α-Syn dependent motor function loss in α-Syn overexpressing mice. The observed phenotypes can be possibly explained by activation of microglia cells in the brain through microbiota metabolites (SCFAs), leading to inflammatory reactions, which are known to trigger α-Syn aggregation.
In conclusion, the role of the PNS in neurodegenerative diseases has to be reconceived. Emerging research links gut bacteria to disorders like anxiety, depression, and autism already. Unravelling the role of gut bacteria in neurodegenerative diseases might eventually offer new chances for treatment of those.
The study is available via the following link:
http://www.cell.com/cell/abstract/S0092-8674(16)31590-2
Image copyright for "picture neuron": Taylor Maley/flickr/CC BY
Image copyright for "picture intestine": Hey Paul Studios/flickr/CC BY
