Pediococcus pentosaceus decreases α-synuclein accumulation and alleviates parkinsonism in Caenorhabditis elegans and Oryzias latipes

In Parkinson's disease (PD), α-synuclein (α-syn) accumulation drives neuropathological progression, establishing it as a potential therapeutic target. Lactic acid bacteria (LAB) provide various health benefits to the host and are expected to offer protective effects on neurological functions through the brain–gut connection, as indicated by animal studies. However, the protective effects of LAB against α-syn are not well understood. We investigated whether LAB feeding could reduce α-syn accumulation and improve mobility in transgenic Caenorhabditis elegans , an invertebrate model organism that expresses human α-syn. Among the nine screened strains, Pediococcus pentosaceus MCRI-640 suppressed α-syn accumulation and the decrease in bending counts, a locomotion index in nematodes. Additionally, feeding P. pentosaceus MCRI-640 to Oryzias latipes (medaka), a vertebrate model organism, alleviated PD-like behavioral defects induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). P. pentosaseus acts as a probiotic against PD, and PD model worms and medaka can be used to screen effective LAB for prevention. • Pediococcus pentosaceus suppressed αSyn accumulation in nematodes. • P. pentosaceus alleviated Parkinson's disease(PD)-like behavioral defects in medaka. • P. pentosaceus acted as a probiotic for PD in animal models. • Probiotics could improve the quality of life of patients with PD.