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

Background: 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 inflammationmediated 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. Aim: 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 in neuroinflammation and oxidative stress. We conclude that the neurodetrimental effects of western diet (WD) and the neu-roprotective effects of Mediterranean diets should be further explored in 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-oxidative effects in PD via improved mitochondrial dynamics and homeostasis, thus reducing PD-related conse-quences. However, there is a significant unmet need for randomized clinical trials to investigate the effec-tiveness of microbial products, probiotic-based supplementation, and dietary intervention in reversing gut microbial dysbiosis in PD.& COPY; 2023 The Authors. Published by Elsevier B.V. on behalf of Cairo University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Automated summary

Parkinson's disease (PD) is caused by ⍺-synuclein aggregation-mediated dopaminergic neuronal loss, leading to motor and non-motor symptoms. Inflammation-mediated oxidative stress, mitochondrial dysfunction, and cytokine-induced toxicity are believed to be involved in the neuronal damage and loss associated with PD. The gut and brain have been found to play important roles in the pathogenesis of PD. This review summarizes the impact of gut microbiome alterations on PD pathogenesis and proposes early interventions and dietary modifications as potential protective measures against PD development.