To uncover the host response pathways that are modified by a B. subtilis diet and that may provide the protective effect against α-synuclein aggregation, we performed comparative global transcriptomics analysis using next generation RNA sequencing (RNA-seq). We compared young adult animals fed on three different diets, E. coli OP50 and B. subtilis PXN21 lawns, consisting of both spores and vegetative cells, and a mixture of both bacteria.
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.