Journal of Advanced Research ( IF 11.4 ) Pub Date : 2022-11-01 , DOI: 10.1016/j.jare.2022.10.013 Safa Salim 1 , Fatima Ahmad 1 , Ayesha Banu 1 , Farhan Mohammad 1
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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 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.
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 neuroprotective 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 consequences. However, there is a significant unmet need for randomized clinical trials to investigate the effectiveness of microbial products, probiotic-based supplementation, and dietary intervention in reversing gut microbial dysbiosis in PD.
中文翻译：
肠道微生物组与帕金森病：发病机制和治疗的视角
背景
帕金森病（PD）是一种黑质致密部中⍺-突触核蛋白聚集介导的多巴胺能神经元丢失的疾病，可导致运动和非运动症状。通过过去二十年的研究，人们越来越认识到炎症介导的氧化应激、线粒体功能障碍和细胞因子诱导的毒性主要涉及与帕金森病相关的神经元损伤和损失。然而，目前尚不清楚这些机制与散发性帕金森病（一种更常见的帕金森病形式）有何关系。肠道和中枢神经系统都与散发性帕金森病的发病机制有关，因此凸显了肠道和大脑之间的相互作用。
目的
综述：在这篇综述中，我们总结了肠道微生物组的改变如何影响帕金森病的发病机制。我们强调了增加/减少帕金森病发展风险的各种机制。根据之前的支持证据，我们建议早期干预措施如何预防帕金森病的发展，以及如何控制特定因素（包括我们的饮食）可以改变我们对疾病机制和治疗的看法。 我们通过描述神经炎症和氧化应激涉及的多种机制来解释帕金森病受试者肠道微生物群与大脑之间的密切关系。 我们的结论是，应该通过临床试验在人体中进一步探讨西方饮食（WD）的神经有害作用和地中海饮食的神经保护作用。
综述的关键科学概念：肠道微生物组和相关代谢物的改变可能导致帕金森病的发病机制。在一些研究中，益生菌已被证明可以通过改善线粒体动力学和稳态来对帕金森病发挥抗氧化作用，从而减少帕金森病相关的后果。然而，随机临床试验的需求尚未得到满足，以研究微生物产品、益生菌补充剂和饮食干预在逆转帕金森病肠道微生物失调方面的有效性。
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