Blood-Mediated Gut–Brain Axis in Parkinson’s Disease: Focus on α-Synuclein Transport and Microbiota Dysbiosis-Induced Inflammation

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons and the deposition of Lewy bodies (LBs). The gut–brain axis has emerged as a potential route for the bidirectional dissemination of PD pathology, in which the enteric and central nervous systems may contribute to the spread of misfolded α-synuclein (α-Syn) and associated neuroinflammatory responses. However, neural pathways alone may not fully account for the widespread distribution of PD pathology across the brain and gut. As another major conduit connecting the gut and the brain, the peripheral circulation may provide an additional route for PD-related pathological processes. Nevertheless, how blood circulation contributes to the development and dissemination of pathology along the gut–brain axis remains underexplored. Accordingly, this narrative review examines peripheral blood as a potential additional route for pathological communication along the gut–brain axis, focusing on two potential mechanisms involving the transport of pathological α-Syn aggregates between the gut and the brain and the circulation of inflammatory signals associated with gut microbiota dysbiosis. Furthermore, to highlight the translational relevance of the gut–blood–brain axis, we briefly summarize recent advances in related blood-derived biomarkers and therapeutic strategies targeting these pathways.