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伴有快速眼动睡眠障碍的帕金森病患者粪便微生物群和血浆代谢组的改变

Alterations of fecal microbiota and plasma metabolome in patients with Parkinson's disease with rapid eye movement sleep disorder.

作者信息

Li Yangdanyu, Liu Yuning, Li Fujia, Liu Xu, Zhang Zixuan, Li Jinyu, Cui Guiyun, Xu Chuanying

机构信息

Department of Neurology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.

出版信息

mSphere. 2025 Jun 25;10(6):e0059024. doi: 10.1128/msphere.00590-24. Epub 2025 May 9.


DOI:10.1128/msphere.00590-24
PMID:40340433
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12188741/
Abstract

UNLABELLED: Patients with Parkinson's disease (PD) with probable rapid eye movement sleep behavior disorder (RBD) (PD-RBD), a specific subtype of PD, are characterized by the presence of more severe motor and non-motor symptoms. This study aimed to elucidate the characteristics and interactions of gut microbiota and plasma metabolic characteristics of PD-RBD, thus screening for the disease mechanisms. A total of 100 PD patients, 50 healthy controls (HCs) and 16 probable idiopathic RBD (iRBD) patients were collected. There were 33 PD-RBD and 67 patients without probable RBD (PD-nRBD) in PD patients. DNA extraction, PCR amplification, and high-throughput sequencing were used for intestinal microbiota analysis, and ultra-high liquid chromatography tandem mass spectrometry was used for metabolome analysis. Spearman analysis was applied to investigate the correlation of fecal microbiota and plasma metabolome. Our findings revealed e ( = 0.017), ( = 0.017), ( = 0.018), ( = 0.035), R-7 group ( = 0.035), and ( = 0.035) were significantly different in PD-RBD, PD-nRBD, and HC. Moreover, the differential metabolites identified in both PD-nRBD and PD-RBD were 3-hydroxy-2-methylpyridine-4,5-dicarboxylate (VIP = 5.802) and 3-methoxy-4-hydroxyphenylglycol sulfate (VIP = 5.732). Furthermore, our analysis revealed that 3-methoxy-4-hydroxyphenylglycol sulfate showed a positive correlation with ( = 0.197, = 0.049). Finally, functional analysis indicated that these distinctive microbiota and metabolites were primarily associated with phenylalanine metabolism and vitamin B6 metabolism. We managed to show that the differential microbiota, differential metabolites, and their interactions in PD-RBD compared to PD-nRBD and HC. This furthers our understanding of disease pathogenesis, and offers fresh perspectives on its detection and treatment. IMPORTANCE: There are currently fewer investigations on the intestinal microbiota and metabolites of probable rapid eye movement sleep behavior disorder (PD-RBD) and idiopathic RBD (iRBD). Our findings indicate that PD-RBD exhibits an increase in and 3-methoxy-4-hydroxyphenethyleneglycol sulfate, and that iRBD exhibits a similar trend. This suggests that the PD prodromal stage may have seen this alteration. Furthermore, functional analysis indicated that these distinctive microbiota and metabolites were primarily associated with phenylalanine metabolism and vitamin B6 metabolism. Basic experiments and multi-center, large-cohort clinical researches are worth conducting to confirm this, since they may offer insights for treating individuals with PD-RBD.

摘要

未标注:帕金森病(PD)合并快速眼动睡眠行为障碍(RBD)(PD-RBD)的患者,这是PD的一种特定亚型,其特征是存在更严重的运动和非运动症状。本研究旨在阐明PD-RBD患者肠道微生物群的特征及其与血浆代谢特征的相互作用,从而筛查疾病机制。共收集了100例PD患者、50例健康对照(HC)和16例疑似特发性RBD(iRBD)患者。PD患者中,有33例为PD-RBD,67例为无RBD可能的患者(PD-nRBD)。采用DNA提取、PCR扩增和高通量测序进行肠道微生物群分析,采用超高效液相色谱串联质谱进行代谢组分析。应用Spearman分析研究粪便微生物群与血浆代谢组的相关性。我们的研究结果显示,R-7组(P = 0.035)、……(此处原文部分信息缺失,按完整原文应为多个指标)在PD-RBD、PD-nRBD和HC组中存在显著差异。此外,在PD-nRBD和PD-RBD中均鉴定出的差异代谢物为3-羟基-2-甲基吡啶-4,5-二羧酸(VIP = 5.802)和3-甲氧基-4-羟基苯乙二醇硫酸盐(VIP = 5.732)。此外,我们的分析表明,3-甲氧基-4-羟基苯乙二醇硫酸盐与……(此处原文部分信息缺失,按完整原文应为某个指标)呈正相关(P = 0.197,r = 0.049)。最后,功能分析表明,这些独特的微生物群和代谢物主要与苯丙氨酸代谢和维生素B6代谢相关。我们成功地展示了与PD-nRBD和HC相比,PD-RBD中存在差异的微生物群、差异代谢物及其相互作用。这进一步加深了我们对疾病发病机制的理解,并为其检测和治疗提供了新的视角。 重要性:目前关于疑似快速眼动睡眠行为障碍(PD-RBD)和特发性RBD(iRBD)的肠道微生物群和代谢物的研究较少。我们的研究结果表明,PD-RBD患者的……(此处原文部分信息缺失,按完整原文应为某个指标)和3-甲氧基-4-羟基苯乙二醇硫酸盐增加,iRBD患者也呈现类似趋势。这表明在PD前驱期可能已经出现了这种改变。此外,功能分析表明,这些独特的微生物群和代谢物主要与苯丙氨酸代谢和维生素B6代谢相关。由于这可能为治疗PD-RBD患者提供思路,因此值得开展基础实验和多中心、大样本队列临床研究来证实这一点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6afc/12188741/490974b38c9d/msphere.00590-24.f005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6afc/12188741/eb4d86d3e938/msphere.00590-24.f001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6afc/12188741/ec5cc2a1d439/msphere.00590-24.f002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6afc/12188741/ce2b2e811fd1/msphere.00590-24.f003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6afc/12188741/011ba568beed/msphere.00590-24.f004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6afc/12188741/490974b38c9d/msphere.00590-24.f005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6afc/12188741/eb4d86d3e938/msphere.00590-24.f001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6afc/12188741/ec5cc2a1d439/msphere.00590-24.f002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6afc/12188741/ce2b2e811fd1/msphere.00590-24.f003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6afc/12188741/011ba568beed/msphere.00590-24.f004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6afc/12188741/490974b38c9d/msphere.00590-24.f005.jpg

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本文引用的文献

[1]
The ketamine metabolite (2R,6R)-hydroxynorketamine rescues hippocampal mRNA translation, synaptic plasticity and memory in mouse models of Alzheimer's disease.

Alzheimers Dement. 2024-8

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