Abstract

The concept of a ‘microbiota-gut-brain axis’ has recently emerged as an important player in the pathophysiology of Parkinson disease (PD), not least because of the reciprocal interaction between gut bacteria and medications. The gut microbiota can influence levodopa kinetics, and conversely, drugs administered for PD can influence gut microbiota composition. Through a two-step enzymatic pathway, gut microbes can decarboxylate levodopa to dopamine in the small intestine and then dehydroxylate it to m-tyramine, thus reducing availability. Inhibition of bacterial decarboxylation pathways could therefore represent a strategy to increase levodopa absorption. Other bacterial perturbations common in PD, such as small intestinal bacterial overgrowth and Helicobacter pylori infection, can also modulate levodopa metabolism, and eradication therapies may improve levodopa absorption. Interventions targeting the gut microbiota offer a novel opportunity to manage disabling motor complications and dopa-unresponsive symptoms. Mediterranean diet-induced changes in gut microbiota composition might improve a range of non-motor symptoms. Prebiotics can increase levels of short-chain fatty acid-producing bacteria and decrease pro-inflammatory species, with positive effects on clinical symptoms and levodopa kinetics. Different formulations of probiotics showed beneficial outcomes on constipation, with some of them improving dopamine levels; however, the most effective dosage and duration and long-term effects of these treatments remain unknown. Data from faecal microbiota transplantation studies are preliminary, but show encouraging trends towards improvement in both motor and non-motor outcomes.

This article summarises the most up-to-date knowledge in pharmacomicrobiomics in PD, and discusses how the manipulation of gut microbiota represents a potential new therapeutic avenue for PD.

中文翻译：

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帕金森病的肠道微生物群：与药物的相互作用及其治疗应用的潜力

摘要

“微生物群-肠-脑轴”的概念最近在帕金森病（PD）的病理生理学中发挥着重要作用，尤其是因为肠道细菌和药物之间的相互作用。肠道微生物群可以影响左旋多巴动力学，相反，治疗帕金森病的药物可以影响肠道微生物群的组成。通过两步酶促途径，肠道微生物可以在小肠中将左旋多巴脱羧为多巴胺，然后将其脱羟基为间酪胺，从而降低可用性。因此，抑制细菌脱羧途径可能是增加左旋多巴吸收的一种策略。 PD 中常见的其他细菌扰动，例如小肠细菌过度生长和幽门螺杆菌感染，也可以调节左旋多巴代谢，根除治疗可能会改善左旋多巴的吸收。针对肠道微生物群的干预措施为控制致残性运动并发症和多巴无反应症状提供了新的机会。地中海饮食引起的肠道微生物群组成的变化可能会改善一系列非运动症状。益生元可以增加产生短链脂肪酸的细菌水平并减少促炎菌，对临床症状和左旋多巴动力学产生积极影响。不同配方的益生菌对便秘显示出有益的效果，其中一些可以改善多巴胺水平；然而，这些治疗的最有效剂量、持续时间和长期效果仍然未知。粪便微生物群移植研究的数据是初步的，但显示出运动和非运动结果改善的令人鼓舞的趋势。

本文总结了帕金森病药物微生物组学的最新知识，并讨论了肠道微生物群的调控如何代表帕金森病的潜在新治疗途径。