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Background: There is strong support from studies in humans and in animal models that Parkinson's disease (PD) may begin in the gut. This brings about a unique opportunity for researchers in the field of neurogastroenterology to contribute to advancing the field and making contributions that could lead to the ability to diagnose and treat PD in the premotor stages. Lack of familiarity with some of the aspects of the experimental approaches used in these studies may present a barrier for neurogastroenterology researchers to enter the field. Much remains to be understood about intestinal-specific components of gut-first PD pathogenesis and the field would benefit from contributions of enteric and central nervous system neuroscientists., Purpose: To address these issues, we have conducted a systematic review of the two most frequently used experimental models of gut-first PD: transneuronal propagation of α-synuclein preformed fibrils and oral exposure to environmental toxins. We have reviewed the details of these studies and present methodological considerations for the use of these models. Our aim is that this review will serve as a framework and useful reference for neuroscientists, gastroenterologists, and neurologists interested in applying their expertise to advancing our understanding of gut-first PD., (© 2023 John Wiley & Sons Ltd.)