{"title":"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","authors":"","doi":"10.1007/s40263-024-01073-4","DOIUrl":null,"url":null,"abstract":"<h3>Abstract</h3> <p>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 <em>m</em>-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 <em>Helicobacter pylori</em> 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.</p> <p>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.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":null,"pages":null},"PeriodicalIF":7.4000,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"The Gut Microbiota in Parkinson Disease: Interactions with Drugs and Potential for Therapeutic Applications\",\"authors\":\"\",\"doi\":\"10.1007/s40263-024-01073-4\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<h3>Abstract</h3> <p>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 <em>m</em>-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 <em>Helicobacter pylori</em> 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.</p> <p>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.</p>\",\"PeriodicalId\":10508,\"journal\":{\"name\":\"CNS drugs\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":7.4000,\"publicationDate\":\"2024-04-03\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"CNS drugs\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s40263-024-01073-4\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"CNS drugs","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s40263-024-01073-4","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
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.
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.