Gut microbiome and Parkinson's disease: Perspective on pathogenesis and treatment

[Display omitted] •The crosstalk between the gut and the brain serves as a route for the spread of PD pathology in a bottom-up or top-down manner.•Gut dysbiosis is evident in PD patients and animal models and is associated with alterations in gut-derived microbial products and immune pathways promoting disease pathology.•Diet induces changes in the GM, with western diet evoking and Mediterranean diet preventing neuroinflammation and neurodegeneration associated with PD.•Gut-derived microbial products can be involved in the regulation of the immune system, the inflammation of both the intestine and the brain, and the integrity of intestinal epithelium and blood–brain barrier (BBB).•Therapeutic strategies that function by reversing gut dysbiosis and mitochondrial dysfunction may prove beneficial to treat PD pathology. Parkinson's disease (PD) is a disease of ⍺-synuclein aggregation-mediated dopaminergic neuronal loss in the substantia nigra pars compacta, which leads to motor and non-motor symptoms. Through the last two decades of research, there has been growing consensus that inflammation-mediated oxidative stress, mitochondrial dysfunction, and cytokine-induced toxicity are mainly involved in neuronal damage and loss associated with PD. However, it remains unclear how these mechanisms relate to sporadic PD, a more common form of PD. Both enteric and central nervous systems have been implicated in the pathogenesis of sporadic PD, thus highlighting the crosstalk between the gut and brain. of Review: In this review, we summarize how alterations in the gut microbiome can affect PD pathogenesis. We highlight various mechanisms increasing/decreasing the risk of PD development. Based on the previous supporting evidence, we suggest how early interventions could protect against PD development and how controlling specific factors, including our diet, could modify our perspective on disease mechanisms and therapeutics. We explain the strong relationship between the gut microbiota and the brain in PD subjects, by delineating the multiple mechanisms involved inneuroinflammation and oxidative stress. We conclude that the neurodetrimental effects of western diet (WD) and the neuroprotective effects of Mediterranean diets should be further exploredin humans through clinical trials. Key Scientific Concepts of Review: Alterations in the gut microbiome and associated metabolites may contribute to pathogenesis in PD. In some studies, probiotics have been shown to exert anti-