Abstract

Parkinson’s disease (PD) is an increasingly common neurodegenerative disease. It has been suggested that the etiology of idiopathic PD is complex and multifactorial involving environmental contributions, such as viral or bacterial infections and microbial dysbiosis, in genetically predisposed individuals. With advances in our understanding of the gut-brain axis, there is increasing evidence that the intestinal microbiota and the mammalian immune system functionally interact. Recent findings suggest that a shift in the gut microbiome to a pro-inflammatory phenotype may play a role in PD onset and progression. While there are links between gut bacteria, inflammation, and PD, the bacterial products involved and how they traverse the gut lumen and distribute systemically to trigger inflammation are ill-defined. Mechanisms emerging in other research fields point to a role for small, inherently stable vesicles released by Gram-negative bacteria, called outer membrane vesicles in disease pathogenesis. These vesicles facilitate communication between bacteria and the host and can shuttle bacterial toxins and virulence factors around the body to elicit an immune response in local and distant organs. In this perspective article, we hypothesize a role for bacterial outer membrane vesicles in PD pathogenesis. We present evidence suggesting that these outer membrane vesicles specifically from Gram-negative bacteria could potentially contribute to PD by traversing the gut lumen to trigger local, systemic, and neuroinflammation. This perspective aims to facilitate a discussion on outer membrane vesicles in PD and encourage research in the area, with the goal of developing strategies for the prevention and treatment of the disease.

中文翻译：

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细菌外膜囊泡是否会导致帕金森病的慢性炎症？

摘要

帕金森病（PD）是一种日益常见的神经退行性疾病。有人认为，特发性帕金森病的病因复杂且多因素，涉及环境影响，例如遗传易感个体的病毒或细菌感染和微生物失调。随着我们对肠脑轴的了解不断深入，越来越多的证据表明肠道微生物群和哺乳动物免疫系统在功能上相互作用。最近的研究结果表明，肠道微生物组向促炎表型的转变可能在帕金森病的发病和进展中发挥作用。虽然肠道细菌、炎症和帕金森病之间存在联系，但所涉及的细菌产物以及它们如何穿过肠腔并全身分布以引发炎症尚不清楚。其他研究领域出现的机制表明，革兰氏阴性菌释放的小型、固有稳定的囊泡（称为外膜囊泡）在疾病发病机制中发挥着作用。这些囊泡促进细菌和宿主之间的沟通，并可以在体内传递细菌毒素和毒力因子，从而引发局部和远处器官的免疫反应。在这篇前瞻性文章中，我们假设细菌外膜囊泡在 PD 发病机制中发挥作用。我们提供的证据表明，这些专门来自革兰氏阴性细菌的外膜囊泡可能通过穿过肠腔引发局部、全身和神经炎症，从而可能导致帕金森病。这一观点旨在促进对帕金森病外膜囊泡的讨论，并鼓励该领域的研究，目标是制定预防和治疗该疾病的策略。