Comprehensive review of in vitro gut-brain axis models in Parkinson’s disease research

This systematic review critically evaluates in vitro gut-brain axis models based on their effectiveness in advancing treatment strategies for Parkinson’s disease (PD). Models such as microfluidic devices, combined organ-on-a-chips (OOCs), and gut-brain organoids are analyzed for their ability to replicate key PD mechanisms, including intestinal barrier dysfunction, microbial dysbiosis, and α-synuclein aggregation. While these models are prospective tools in isolating facets of PD pathology such as microbiota modulation, neurotoxin transport, and neuroinflammation mitigation, challenges remain in their physiological relevance, scalability, and translational potential. This review discusses the designs and limitations of the latest in vitro models and identifies areas that may enhance their utility in developing effective treatments for PD.