Jiang-Mei Gao
Multiomics of parkinsonism cynomolgus monkeys highlights significance of metabolites in interaction between host and microbiota
Gao, Jiang-Mei; Xia, Shou-Yue; Hide, Geoff; Li, Bi-Hai; Liu, Yi-Yan; Wei, Zhi-Yuan; Zhuang, Xiao-Ji; Yan, Qing; Wang, Yun; Yang, Wei; Chen, Jian-Huan; Rao, Jun-Hua
Authors
Shou-Yue Xia
Prof Geoff Hide G.Hide@salford.ac.uk
Professor
Bi-Hai Li
Yi-Yan Liu
Zhi-Yuan Wei
Xiao-Ji Zhuang
Qing Yan
Yun Wang
Wei Yang
Jian-Huan Chen
Jun-Hua Rao
Contributors
Prof Geoff Hide G.Hide@salford.ac.uk
Project Member
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.
Citation
Gao, J.-M., Xia, S.-Y., Hide, G., Li, B.-H., Liu, Y.-Y., Wei, Z.-Y., …Rao, J.-H. (2024). Multiomics of parkinsonism cynomolgus monkeys highlights significance of metabolites in interaction between host and microbiota. npj Biofilms and Microbiomes, 10(1), 61. https://doi.org/10.1038/s41522-024-00535-3
Journal Article Type | Article |
---|---|
Acceptance Date | Jul 18, 2024 |
Online Publication Date | Jul 26, 2024 |
Publication Date | Jul 26, 2024 |
Deposit Date | Jul 30, 2024 |
Publicly Available Date | Aug 2, 2024 |
Journal | npj Biofilms and Microbiomes |
Publisher | Nature Publishing Group |
Peer Reviewed | Peer Reviewed |
Volume | 10 |
Issue | 1 |
Pages | 61 |
DOI | https://doi.org/10.1038/s41522-024-00535-3 |
Publisher URL | https://www.nature.com/articles/s41522-024-00535-3 |
Files
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Publisher Licence URL
http://creativecommons.org/licenses/by/4.0/
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