元基因组分析揭示了帕金森病患者肠道微生物组的大规模破坏。

IF 7.4 1区医学 Q1 CLINICAL NEUROLOGY

Movement Disorders Pub Date : 2024-08-28 DOI:10.1002/mds.29959

Avril Metcalfe-Roach PhD, Mihai S. Cirstea PhD, Adam C. Yu MSc, Hena R. Ramay PhD, Olabisi Coker PhD, Seti Boroomand PhD, Faezeh Kharazyan MSc, Davide Martino MD, Laura K. Sycuro PhD, Silke Appel-Cresswell MD, B. Brett Finlay PhD

{"title":"元基因组分析揭示了帕金森病患者肠道微生物组的大规模破坏。","authors":"Avril Metcalfe-Roach PhD, Mihai S. Cirstea PhD, Adam C. Yu MSc, Hena R. Ramay PhD, Olabisi Coker PhD, Seti Boroomand PhD, Faezeh Kharazyan MSc, Davide Martino MD, Laura K. Sycuro PhD, Silke Appel-Cresswell MD, B. Brett Finlay PhD","doi":"10.1002/mds.29959","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Background</h3>\n \n <p>Parkinson's disease (PD) has been consistently linked to alterations within the gut microbiome.</p>\n </section>\n \n <section>\n \n <h3> Objective</h3>\n \n <p>Our goal was to identify microbial features associated with PD incidence and progression.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>Metagenomic sequencing was used to characterize taxonomic and functional changes to the PD microbiome and to explore their relation to bacterial metabolites and disease progression. Motor and non-motor symptoms were tracked using Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) and levodopa equivalent dose across ≤5 yearly study visits. Stool samples were collected at baseline for metagenomic sequencing (176 PD, 100 controls).</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>PD-derived stool samples had reduced intermicrobial connectivity and seven differentially abundant species compared to controls. A suite of bacterial functions differed between PD and controls, including depletion of carbohydrate degradation pathways and enrichment of ribosomal genes. <i>Faecalibacterium prausnitzii</i>-specific reads contributed significantly to more than half of all differentially abundant functional terms. A subset of disease-associated functional terms correlated with faster progression of MDS-UPDRS part IV and separated those with slow and fast progression with moderate accuracy within a random forest model (area under curve = 0.70). Most PD-associated microbial trends were stronger in those with symmetric motor symptoms.</p>\n </section>\n \n <section>\n \n <h3> Conclusion</h3>\n \n <p>We provide further evidence that the PD microbiome is characterized by reduced intermicrobial communication and a shift to proteolytic metabolism in lieu of short-chain fatty acid production, and suggest that these microbial alterations may be relevant to disease progression. We also describe how our results support the existence of gut-first versus brain-first PD subtypes. © 2024 The Author(s). <i>Movement Disorders</i> published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.</p>\n </section>\n </div>","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"39 10","pages":"1740-1751"},"PeriodicalIF":7.4000,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mds.29959","citationCount":"0","resultStr":"{\"title\":\"Metagenomic Analysis Reveals Large-Scale Disruptions of the Gut Microbiome in Parkinson's Disease\",\"authors\":\"Avril Metcalfe-Roach PhD, Mihai S. Cirstea PhD, Adam C. Yu MSc, Hena R. Ramay PhD, Olabisi Coker PhD, Seti Boroomand PhD, Faezeh Kharazyan MSc, Davide Martino MD, Laura K. Sycuro PhD, Silke Appel-Cresswell MD, B. Brett Finlay PhD\",\"doi\":\"10.1002/mds.29959\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Background</h3>\\n \\n <p>Parkinson's disease (PD) has been consistently linked to alterations within the gut microbiome.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Objective</h3>\\n \\n <p>Our goal was to identify microbial features associated with PD incidence and progression.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>Metagenomic sequencing was used to characterize taxonomic and functional changes to the PD microbiome and to explore their relation to bacterial metabolites and disease progression. Motor and non-motor symptoms were tracked using Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) and levodopa equivalent dose across ≤5 yearly study visits. Stool samples were collected at baseline for metagenomic sequencing (176 PD, 100 controls).</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>PD-derived stool samples had reduced intermicrobial connectivity and seven differentially abundant species compared to controls. A suite of bacterial functions differed between PD and controls, including depletion of carbohydrate degradation pathways and enrichment of ribosomal genes. <i>Faecalibacterium prausnitzii</i>-specific reads contributed significantly to more than half of all differentially abundant functional terms. A subset of disease-associated functional terms correlated with faster progression of MDS-UPDRS part IV and separated those with slow and fast progression with moderate accuracy within a random forest model (area under curve = 0.70). Most PD-associated microbial trends were stronger in those with symmetric motor symptoms.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Conclusion</h3>\\n \\n <p>We provide further evidence that the PD microbiome is characterized by reduced intermicrobial communication and a shift to proteolytic metabolism in lieu of short-chain fatty acid production, and suggest that these microbial alterations may be relevant to disease progression. We also describe how our results support the existence of gut-first versus brain-first PD subtypes. © 2024 The Author(s). <i>Movement Disorders</i> published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.</p>\\n </section>\\n </div>\",\"PeriodicalId\":213,\"journal\":{\"name\":\"Movement Disorders\",\"volume\":\"39 10\",\"pages\":\"1740-1751\"},\"PeriodicalIF\":7.4000,\"publicationDate\":\"2024-08-28\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mds.29959\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Movement Disorders\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/mds.29959\",\"RegionNum\":1,\"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":"Movement Disorders","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/mds.29959","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}

引用次数: 0

摘要

背景：帕金森病（PD）一直与肠道微生物组的改变有关：帕金森病（PD）一直与肠道微生物组的改变有关：我们的目标是确定与帕金森病发病率和进展相关的微生物特征：元基因组测序用于描述帕金森病微生物组的分类和功能变化，并探讨它们与细菌代谢物和疾病进展的关系。使用运动障碍协会统一帕金森病评定量表（MDS-UPDRS）和左旋多巴当量剂量对运动和非运动症状进行跟踪，每年的研究访问次数不超过5次。基线时收集粪便样本进行元基因组测序（176 例帕金森病患者，100 例对照组）：结果：与对照组相比，帕金森病患者粪便样本中微生物间的连通性降低，且有七种不同的丰富物种。腹泻病和对照组的细菌功能存在差异，包括碳水化合物降解途径的减少和核糖体基因的丰富。普氏粪杆菌的特异性读数对一半以上的差异丰富功能项做出了重要贡献。与疾病相关的功能词子集与 MDS-UPDRS 第四部分的快速进展相关，并在随机森林模型中以中等精度（曲线下面积 = 0.70）区分了进展缓慢和进展快速的功能词子集。大多数与帕金森病相关的微生物趋势在有对称性运动症状的患者中更为明显：我们提供了进一步的证据，证明帕金森病微生物组的特点是微生物间交流减少，并转向蛋白水解代谢，而不是短链脂肪酸的生产，并表明这些微生物的改变可能与疾病的进展有关。我们还描述了我们的研究结果如何支持存在肠道优先与大脑优先的帕金森病亚型。© 2024 作者简介运动障碍》由 Wiley Periodicals LLC 代表国际帕金森和运动障碍协会出版。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Metagenomic Analysis Reveals Large-Scale Disruptions of the Gut Microbiome in Parkinson's Disease

查看原文本刊更多论文

Metagenomic Analysis Reveals Large-Scale Disruptions of the Gut Microbiome in Parkinson's Disease

Background

Parkinson's disease (PD) has been consistently linked to alterations within the gut microbiome.

Objective

Our goal was to identify microbial features associated with PD incidence and progression.

Methods

Metagenomic sequencing was used to characterize taxonomic and functional changes to the PD microbiome and to explore their relation to bacterial metabolites and disease progression. Motor and non-motor symptoms were tracked using Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) and levodopa equivalent dose across ≤5 yearly study visits. Stool samples were collected at baseline for metagenomic sequencing (176 PD, 100 controls).

Results

PD-derived stool samples had reduced intermicrobial connectivity and seven differentially abundant species compared to controls. A suite of bacterial functions differed between PD and controls, including depletion of carbohydrate degradation pathways and enrichment of ribosomal genes. Faecalibacterium prausnitzii-specific reads contributed significantly to more than half of all differentially abundant functional terms. A subset of disease-associated functional terms correlated with faster progression of MDS-UPDRS part IV and separated those with slow and fast progression with moderate accuracy within a random forest model (area under curve = 0.70). Most PD-associated microbial trends were stronger in those with symmetric motor symptoms.

Conclusion

We provide further evidence that the PD microbiome is characterized by reduced intermicrobial communication and a shift to proteolytic metabolism in lieu of short-chain fatty acid production, and suggest that these microbial alterations may be relevant to disease progression. We also describe how our results support the existence of gut-first versus brain-first PD subtypes. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

求助全文

通过发布文献求助，成功后即可免费获取论文全文。去求助

来源期刊

Movement Disorders 医学-临床神经学

CiteScore

13.30

自引率

8.10%

发文量

371

审稿时长

12 months

期刊介绍： Movement Disorders publishes a variety of content types including Reviews, Viewpoints, Full Length Articles, Historical Reports, Brief Reports, and Letters. The journal considers original manuscripts on topics related to the diagnosis, therapeutics, pharmacology, biochemistry, physiology, etiology, genetics, and epidemiology of movement disorders. Appropriate topics include Parkinsonism, Chorea, Tremors, Dystonia, Myoclonus, Tics, Tardive Dyskinesia, Spasticity, and Ataxia.