In summary, this study demonstrated that a ‘two-hit” PD mouse model (SNCA mice given LPS or DSP-4 injection) were more susceptible to PD development than “one-hit” PD model (WT mice given LPS or DSP-4 injection), as evidenced by motor dysfunction, dopaminergic neuron loss, inflammatory gene expression in the colon, and the disruption of gut microbiota. Here, DUSP26 is linked to Parkinson disease.