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    Probiotic Bacillus subtilis Protects against alpha-Synuclein Aggregation in C. elegans

    Year: 2020

    Journal: Cell Reports, Volume 30, JAN 14, page 367

    Authors: Goya, Maria Eugenia; Xue, Feng; Sampedro-Torres-Quevedo, Cristina; Arnaouteli, Sofia; Riquelme-Dominguez, Lourdes; Romanowski, Andres; Brydon, Jack; Ball, Kathryn L.; Stanley-Wall, Nicola R.; Doitsidou, Maria

    Organizations: EMBOEuropean Molecular Biology Organization (EMBO) [ALTF 529-2017]; Parkinson's UK, United Kingdom [PRO-17-21]; BBSRC, United KingdomUK Research & Innovation (UKRI)Biotechnology and Biological Sciences Research Council (BBSRC) [BB/P001335/1, BB/R50614X/1]; Wellcome Trust-University of Edinburgh Institutional Strategic Support Fund ISSF3 award; NIH Office of Research Infrastructure ProgramsUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [P40 OD010440]; National Science FoundationNational Science Foundation (NSF) [1756219]; Gene Knockout Project at the Oklahoma Medical Research Foundation; Muir Maxwell Epilepsy Centre; [MSCA-IF 798650]

    Recent discoveries have implicated the gut microbiome in the progression and severity of Parkinson's disease; however, how gut bacteria affect such neurodegenerative disorders remains unclear. Here, we report that the Bacillus subtilis probiotic strain PXN21 inhibits alpha-synuclein aggregation and clears preformed aggregates in an established Caenorhabditis elegans model of synucleinopathy. This protection is seen in young and aging animals and is partly mediated by DAF-16. Multiple B. subtilis strains trigger the protective effect via both spores and vegetative cells, partly due to a biofilm formation in the gut of the worms and the release of bacterial metabolites. We identify several host metabolic pathways differentially regulated in response to probiotic exposure, including sphingolipid metabolism. We further demonstrate functional roles of the sphingolipid metabolism genes lagr-1, asm-3, and sptl-3 in the anti-aggregation effect. Our findings provide a basis for exploring the disease-modifying potential of B. subtilis as a dietary supplement.
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