Probiotic Bacillus subtilis Protects against a-Synuclein Aggregation in C. elegans (Goya ME et al., Cell Reports, 2020)

This project contains datasets of z-stack images of C. elegans strains used to study how B. subtilis PXN21 affects α-synuclein aggregation (Goya et al 2020). The background strain NL5901 (van Ham et al 2008) contains chromosomal insertions of YFP fused to the human α-synuclein (pkIs2386[Punc-54::α-synuclein::YFP + unc-119(+)]). The following C. elegans srains were used and/or created for this project:
NL5901 pkIs2386[Punc-54::α-synuclein::YFP + unc-119(+)]
MDH586 daf-2(e1370) III; pkIs2386
MDH585 daf-16(mu86) I; pkIs2386
MDH587 hsf-1(sy441) I; pkIs2386
MDH657 daf-2(e1370) III; daf-16(mu86) I; pkIs2386
MDH614 daf-2(gk390525) III; pkIs2386
MDH611 eat-2(ad465) II; pkIs2386
MDH711 lagr-1(gk331) I, pkIs2386
MDH725 sptl-3(ok1927) II; pkIs2386
MDH724 asm-3(ok1744) IV; pkIs2386.

High magnification (40x objective) z stack images of the head region were obtained by using a Zeiss Axio imager 2 microscope.

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-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.