Periodic Reporting for period 1 - Gut_Fights_PD (Investigating protective mechanisms of gut bacteria in C. elegans models of Parkinson’s disease)
Reporting period: 2019-09-01 to 2021-08-31
In people with Parkinson’s, the protein alpha-synuclein (α-syn) builds up and forms toxic clumps which induce the degeneration of specific dopamine-producing neurons. Using a worm model of PD expressing the α-syn, we tested the effect of commercially available probiotic bacteria in the formation of toxic protein aggregates. We identified a strongly protective effect when worms were fed the strain Bacillus subtilis PXN21 (isolated from Bio-Kult), in comparison to the regular worm’s diet. The main goal of this project was to study how this probiotic induces the protective effect, at the molecular level. We proposed to elucidate this by focusing on both organisms in the interaction: the bacteria and the worms. We aimed to explore the physiological changes induced by B. subtilis in the worms by studying the overall gene expression in the host. From the bacterial side, we proposed to identify specific genes and metabolic pathways used by B. subtilis to reduce protein aggregates by doing a single-gene deletion library screening.
The main results from this project were published in Goya et al, 2020 (https://doi.org/10.1016/j.celrep.2019.12.078). We have extensively communicated our research findings in numerous scientific meetings such us the International C. elegans GSA meeting (2019 and 2021), the UK worm meeting (2019), the Second Latin American Worm Meeting (2020), the European worm meeting (2020), the XXXV Argentinean Society for Research in Neuroscience meeting (2020) and the Ageing in Isolation online seminar series.
As for public dissemination, following our press release from The University of Edinburgh (https://www.ed.ac.uk/biomedical-sciences/news/2018/probiotic-hope-for-parkinsons-disease) our work was featured in Parkinson’s UK, Herald Scotland, Daily Mail UK, Neuroscience News, and iNews, among others. The lab has been involved in multiple events organized by the Edinburgh branch of Parkinson’s UK, which has given further dissemination to our research: https://www.parkinsons.org.uk/news/gut-bacteria-could-guard-against-parkinsons https://www.edinburghparkinsons.org/towards-a-clinical-trial-to-assess-the-ability-of-a-probiotic-bacterium-to-protect-against-%CE%B1-synuclein-aggregation-in-parkinsons/.
All the relevant information about the project can be found in our lab webpage: https://www.ed.ac.uk/discovery-brain-sciences/our-staff/research-groups/maria-doitsidou
More broadly, this project established a worm-bacteria dual model system to study proteostasis and PD that can be extended to find new protective species of the human gut microbiome. In this sense, this project has pioneered the use of C. elegans for microbiome studies and has demonstrated that the potential of this model to help elucidate single-bacterial species effects at the molecular level is endless.