Multiomics of parkinsonism cynomolgus monkeys highlights significance of metabolites in interaction between host and microbiota.

IF 7.8 1区 生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
Jiang-Mei Gao, Shou-Yue Xia, Geoff Hide, Bi-Hai Li, Yi-Yan Liu, Zhi-Yuan Wei, Xiao-Ji Zhuang, Qing Yan, Yun Wang, Wei Yang, Jian-Huan Chen, Jun-Hua Rao
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Abstract

The gut microbiota has been demonstrated to play a significant role in the pathogenesis of Parkinson's disease (PD). However, conflicting findings regarding specific microbial species have been reported, possibly due to confounding factors within human populations. Herein, our current study investigated the interaction between the gut microbiota and host in a non-human primate (NHP) PD model induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) using a multi-omic approach and a self-controlled design. Our transcriptomic sequencing of peripheral blood leukocytes (PBL) identified key genes involved in pro-inflammatory cytokine dysregulation, mitochondrial function regulation, neuroprotection activation, and neurogenesis associated with PD, such as IL1B, ATP1A3, and SLC5A3. The metabolomic profiles in serum and feces consistently exhibited significant alterations, particularly those closely associated with inflammation, mitochondrial dysfunctions and neurodegeneration in PD, such as TUDCA, ethylmalonic acid, and L-homophenylalanine. Furthermore, fecal metagenome analysis revealed gut dysbiosis associated with PD, characterized by a significant decrease in alpha diversity and altered commensals, particularly species such as Streptococcus, Butyrivibrio, and Clostridium. Additionally, significant correlations were observed between PD-associated microbes and metabolites, such as sphingomyelin and phospholipids. Importantly, PDPC significantly reduced in both PD monkey feces and serum, exhibiting strong correlation with PD-associated genes and microbes, such as SLC5A3 and Butyrivibrio species. Moreover, such multi-omic differential biomarkers were linked to the clinical rating scales of PD monkeys. Our findings provided novel insights into understanding the potential role of key metabolites in the host-microbiota interaction involved in PD pathogenesis.

Abstract Image

帕金森病猴的多组学研究凸显了代谢物在宿主与微生物群相互作用中的重要性。
肠道微生物群已被证实在帕金森病(PD)的发病机制中发挥着重要作用。然而,关于特定微生物物种的研究结果却相互矛盾,这可能是由于人类群体中的混杂因素造成的。在此,我们目前的研究采用多组学方法和自控设计,调查了非人灵长类(NHP)帕金森病模型中肠道微生物群与宿主之间的相互作用,该模型由1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)诱发。我们对外周血白细胞(PBL)进行了转录组测序,发现了与帕金森病相关的促炎细胞因子失调、线粒体功能调节、神经保护激活和神经发生的关键基因,如IL1B、ATP1A3和SLC5A3。血清和粪便中的代谢组图谱始终表现出显著的变化,尤其是那些与帕金森病的炎症、线粒体功能障碍和神经变性密切相关的代谢组,如TUDCA、乙基丙二酸和L-高苯丙氨酸。此外,粪便元基因组分析显示了与帕金森病相关的肠道菌群失调,其特点是α多样性显著降低和共生菌发生改变,尤其是链球菌、丁弧菌和梭状芽孢杆菌等物种。此外,还观察到与脊髓灰质炎相关的微生物与代谢物(如鞘磷脂和磷脂)之间存在明显的相关性。重要的是,PD 猴粪便和血清中的 PDPC 都明显减少,这与 PD 相关基因和微生物(如 SLC5A3 和丁弧菌)有很强的相关性。此外,这些多组学差异生物标志物还与帕金森病猴的临床评分量表有关。我们的研究结果为了解关键代谢物在帕金森氏症发病机制所涉及的宿主-微生物群相互作用中的潜在作用提供了新的见解。
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来源期刊
npj Biofilms and Microbiomes
npj Biofilms and Microbiomes Immunology and Microbiology-Microbiology
CiteScore
12.10
自引率
3.30%
发文量
91
审稿时长
9 weeks
期刊介绍: npj Biofilms and Microbiomes is a comprehensive platform that promotes research on biofilms and microbiomes across various scientific disciplines. The journal facilitates cross-disciplinary discussions to enhance our understanding of the biology, ecology, and communal functions of biofilms, populations, and communities. It also focuses on applications in the medical, environmental, and engineering domains. The scope of the journal encompasses all aspects of the field, ranging from cell-cell communication and single cell interactions to the microbiomes of humans, animals, plants, and natural and built environments. The journal also welcomes research on the virome, phageome, mycome, and fungome. It publishes both applied science and theoretical work. As an open access and interdisciplinary journal, its primary goal is to publish significant scientific advancements in microbial biofilms and microbiomes. The journal enables discussions that span multiple disciplines and contributes to our understanding of the social behavior of microbial biofilm populations and communities, and their impact on life, human health, and the environment.
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