Background: Increased gut permeability (leaky gut) and alterations in gut microbiota
are now widely accepted as relevant to the etiology, course and treatment of many
neuropsychiatric disorders, including Parkinson disease (PD). Although a wide array of data
on the biological underpinnings of PD has not yet been linked to such gut-associated
changes, increased gut permeability and dysregulated microbiota alter many pathways germane
Methods: In this article we review and integrate these wider biological changes in PD, including
increased oxidative and nitrosative stress, immune-inflammatory processes, tryptophan
catabolites and alterations in serotoninergic and melatoninergic pathways.
Results: These wider biological changes in PD are compatible with alterations in gut permeability
and changes in gut microbiota. By driving tryptophan down the kynurenine pathway,
pro-inflammatory cytokines and chronic stress-driven activation of the hypothalamic-pituitary-adrenal axis decrease
the availability of serotonin as a precursor for activation of the melatonergic pathways.
Conclusion: Decreased local melatonin synthesis in glia, gut, neuronal and immune cells is likely to be important
to the etiology, course and management of PD.