Two hallmarks of Parkinson’s disease (PD) are the widespread deposition of misfolded alpha-synuclein (αSyn) protein in the nervous system and loss of substantia nigra dopamine neurons. Recent research has suggested that αSyn aggregates in the enteric nervous system (ENS) lead to prodromal gastrointestinal (GI) symptoms such as constipation in PD, then propagating to the brain stem and eventually triggering neurodegeneration and motor symptoms. Additionally, whether the microbiome changes in PD contribute to the primary pathogenesis or, alternatively, are consequential to either the disease process or medication is still unclear. In this review, we discuss the possible roles of αSyn and microbiome changes in the GI system in PD and consider if and how the changes interact and contribute to the disease process and symptoms. CLICK TO REVIEW