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

María Eugenia Goya ME, Xue F, Sampedro-Torres-Quevedo C, Arnaouteli S, Riquelme-Dominguez L, Romanowski A, Brydon J, Ball KL, Stanley-Wall NR, Doitsidou M (2020) Cell Reports 2020 Jan; 30, 2, P367-380.E7, DOI: 10.1016/j.celrep.2019.12.078 

Web URL: Read the article on cell.com here

Abstract:

  • Highlights
  • B. subtilis PXN21 inhibits and reverses α-syn aggregation in a C. elegans model
  • Spores and vegetative cells protect through different mechanisms
  • The probiotic inhibits α-syn aggregation by changing the host sphingolipid metabolism
  • Biofilm formation in the gut and bacterial metabolites reduce α-syn aggregation

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 α-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-1asm-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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