Effects of fecal microbiota transplantation from healthy individuals and PD patients on intestinal microbiota and functional pathways in MPTP-induced mice

Aim Parkinson's disease (PD) is a common neurodegenerative disorder whose pathogenesis is closely associated with the dysfunction of the “gut - brain axis.” This study aimed to investigate the regulatory effects of fecal microbiota transplantation (FMT) from different sources (PD patients vs. healthy individuals) on the gut microbiota structure and predictive functions in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine MPTP-induced PD mouse models. Methods We established acute PD mouse models through the intraperitoneal injection of MPTP and transplanted fecal microbiota from PD patients or healthy donors. The gut microbiota structure was analyzed via 16S rRNA gene sequencing, and functional pathway predictions were performed using PICRUSt2. Result We found that MPTP mice receiving FMT from PD patients (MPTP + PD group) exhibited the highest alpha diversity in their gut microbiota, which was driven by an expansion of opportunistic pathobionts (e.g., Helicobacter, Desulfovibrio) rather than by health-associated commensals. In contrast, MPTP mice receiving FMT from healthy donors (MPTP + HC group) demonstrated the lowest alpha diversity. LEfSe analysis identified inter-group-specific biomarkers, such as the enrichment of opportunistic pathogens in the MPTP + PD group and the enrichment of probiotics in the MPTP + HC group. Functional prediction analysis revealed that healthy donor FMT significantly restored the impaired carbohydrate and energy metabolism pathways in the model mice's gut microbiota, upregulated the pathways related to neurotransmitter precursors metabolism, and reduced the activity of inflammation - related pathways such as lipopolysaccharide synthesis. Conversely, PD patient FMT was associated with the activation of pro-inflammatory and neurodegenerative disease - related functional modules. Conclusion This study demonstrates that FMT derived from healthy individuals can potentially correct the metabolic disturbances and inflammatory states associated with PD by reshaping the functional profile of gut microbiota rather than merely altering its structural diversity. These findings provide critical mechanistic insights and preclinical evidence for microbiome - based PD intervention strategies.