帕金森病肠道宏基因组的综合多队列分析

Integrated Multi-Cohort Analysis of the Parkinson's Disease Gut Metagenome.

作者信息

Boktor Joseph C, Sharon Gil, Verhagen Metman Leo A, Hall Deborah A, Engen Phillip A, Zreloff Zoe, Hakim Daniel J, Bostick John W, Ousey James, Lange Danielle, Humphrey Gregory, Ackermann Gail, Carlin Martha, Knight Rob, Keshavarzian Ali, Mazmanian Sarkis K

机构信息

Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, California, USA.

Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, Maryland, USA.

出版信息

Mov Disord. 2023 Mar;38(3):399-409. doi: 10.1002/mds.29300. Epub 2023 Jan 24.

DOI:10.1002/mds.29300

PMID:36691982

Abstract

BACKGROUND

The gut microbiome is altered in several neurologic disorders, including Parkinson's disease (PD).

OBJECTIVES

The aim is to profile the fecal gut metagenome in PD for alterations in microbial composition, taxon abundance, metabolic pathways, and microbial gene products, and their relationship with disease progression.

METHODS

Shotgun metagenomic sequencing was conducted on 244 stool donors from two independent cohorts in the United States, including individuals with PD (n = 48, n = 47, respectively), environmental household controls (HC, n = 29, n = 30), and community population controls (PC, n = 41, n = 49). Microbial features consistently altered in PD compared to HC and PC subjects were identified. Data were cross-referenced to public metagenomic data sets from two previous studies in Germany and China to determine generalizable microbiome features.

RESULTS

We find several significantly altered taxa between PD and controls within the two cohorts sequenced in this study. Analysis across global cohorts returns consistent changes only in Intestinimonas butyriciproducens. Pathway enrichment analysis reveals disruptions in microbial carbohydrate and lipid metabolism and increased amino acid and nucleotide metabolism in PD. Global gene-level signatures indicate an increased response to oxidative stress, decreased cellular growth and microbial motility, and disrupted intercommunity signaling.

CONCLUSIONS

A metagenomic meta-analysis of PD shows consistent and novel alterations in functional metabolic potential and microbial gene abundance across four independent studies from three continents. These data reveal that stereotypic changes in the functional potential of the gut microbiome are a consistent feature of PD, highlighting potential diagnostic and therapeutic avenues for future research. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

摘要

背景

肠道微生物群在包括帕金森病（PD）在内的多种神经系统疾病中会发生改变。

目的

旨在分析PD患者粪便肠道宏基因组，以了解微生物组成、分类群丰度、代谢途径和微生物基因产物的变化，以及它们与疾病进展的关系。

方法

对来自美国两个独立队列的244名粪便捐赠者进行鸟枪法宏基因组测序，包括PD患者（分别为n = 48、n = 47）、家庭环境对照者（HC，n = 29、n = 30）和社区人群对照者（PC，n = 41、n = 49）。确定与HC和PC受试者相比，PD中持续改变的微生物特征。将数据与之前德国和中国的两项研究的公共宏基因组数据集进行交叉参考，以确定可推广的微生物群特征。

结果

在本研究测序的两个队列中，我们发现PD与对照之间有几个分类群发生了显著改变。对全球队列的分析仅在丁酸肠道单胞菌中发现了一致的变化。通路富集分析显示，PD中微生物碳水化合物和脂质代谢受到破坏，氨基酸和核苷酸代谢增加。全球基因水平特征表明对氧化应激的反应增加、细胞生长和微生物运动性降低以及群落间信号传导中断。