帕金森病中的肠道微生物群:与药物的相互作用及治疗应用潜力

IF 7.4 2区 医学 Q1 CLINICAL NEUROLOGY CNS drugs Pub Date : 2024-04-03 DOI:10.1007/s40263-024-01073-4
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引用次数: 0

摘要

摘要 "微生物群-肠道-大脑轴 "的概念最近已成为帕金森病(PD)病理生理学中的一个重要角色,这主要是因为肠道细菌与药物之间存在相互影响。肠道微生物群会影响左旋多巴的动力学,反之,治疗帕金森病的药物也会影响肠道微生物群的组成。通过两步酶解途径,肠道微生物可在小肠中将左旋多巴脱羧为多巴胺,然后脱羟基为间苯二胺,从而降低左旋多巴的可用性。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。其他常见于帕金森病的细菌紊乱,如小肠细菌过度生长和幽门螺旋杆菌感染,也会调节左旋多巴的代谢,根除细菌的疗法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一个新的机会。由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。益生元能提高短链脂肪酸细菌的水平,减少促炎菌,从而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都有益处,其中一些还能改善多巴胺水平;然而,这些治疗方法的最有效剂量、持续时间和长期效果仍不得而知。粪便微生物群移植研究的数据尚属初步,但显示出运动和非运动结果均有令人鼓舞的改善趋势。本文总结了帕金森病药理微生物组学的最新知识,并讨论了操纵肠道微生物群如何成为治疗帕金森病的潜在新途径。
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The Gut Microbiota in Parkinson Disease: Interactions with Drugs and Potential for Therapeutic Applications

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.

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来源期刊
CNS drugs
CNS drugs 医学-精神病学
CiteScore
12.00
自引率
3.30%
发文量
82
审稿时长
6-12 weeks
期刊介绍: CNS Drugs promotes rational pharmacotherapy within the disciplines of clinical psychiatry and neurology. The Journal includes: - Overviews of contentious or emerging issues. - Comprehensive narrative reviews that provide an authoritative source of information on pharmacological approaches to managing neurological and psychiatric illnesses. - Systematic reviews that collate empirical evidence to answer a specific research question, using explicit, systematic methods as outlined by the PRISMA statement. - Adis Drug Reviews of the properties and place in therapy of both newer and established drugs in neurology and psychiatry. - Original research articles reporting the results of well-designed studies with a strong link to clinical practice, such as clinical pharmacodynamic and pharmacokinetic studies, clinical trials, meta-analyses, outcomes research, and pharmacoeconomic and pharmacoepidemiological studies. Additional digital features (including animated abstracts, video abstracts, slide decks, audio slides, instructional videos, infographics, podcasts and animations) can be published with articles; these are designed to increase the visibility, readership and educational value of the journal’s content. In addition, articles published in CNS Drugs may be accompanied by plain language summaries to assist readers who have some knowledge of, but not in-depth expertise in, the area to understand important medical advances.
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