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.

中文翻译：

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益生菌枯草芽孢杆菌可防止秀丽隐杆线虫中的 α-突触核蛋白聚集。

最近的发现表明肠道微生物组与帕金森病的进展和严重程度有关。然而，肠道细菌如何影响此类神经退行性疾病仍不清楚。在这里，我们报告枯草芽孢杆菌益生菌菌株 PXN21 抑制 α-突触核蛋白聚集并清除已建立的秀丽隐杆线虫突触核蛋白病模型中预先形成的聚集体。这种保护作用见于年轻和老年动物，部分是由 DAF-16 介导的。多种枯草芽孢杆菌菌株通过孢子和营养细胞触发保护作用，部分原因是蠕虫肠道中生物膜的形成和细菌代谢物的释放。我们确定了几种因益生菌暴露而受到差异调节的宿主代谢途径，包括鞘脂代谢。我们进一步证明了鞘脂代谢基因 lagr-1、asm-3 和 sptl-3 在抗聚集作用中的功能作用。我们的研究结果为探索枯草芽孢杆菌作为膳食补充剂的疾病缓解潜力提供了基础。