Aerobic exercise ameliorates gut flora imbalance and attenuates PD-associated pathological impairments and cognitive deficits in PD mice, but its efficacy on non-motor symptoms can be eliminated by antibiotics, and gut flora-mediated aerobic exercise exerts neuroprotective effects on PD by regulating FNDC5 secretion via PGC1-α/CREB. Here, FNDC5 is linked to Parkinson disease.