A lifetime of environmental insults (including Western diets and food additives, nano- and microplastics, pesticides and herbicides, industrial solvents, and air pollution) act on the intestinal microbiome and barrier. These exposures promote microbiota dysbiosis, disrupt tight junctions, and erode the mucus layer, collectively reducing gut resilience. Once this peripheral defense is compromised, several mechanistic pathways propagate pathology to the brain: (a) amyloid seeding by bacterial functional amyloids, (b) maladaptive T cell education and autoimmune responses, (c) microbiome-driven metabolic shifts that generate neurotoxic metabolites and reduce short-chain fatty acids, and (d) systemic inflammatory amplification. Together, these processes lower the threshold for α-syn misfolding, neuroinflammation, and neurodegeneration.