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

Autor: Gao JM; Guangdong Key Laboratory of Animal Conservation and Resource Utilization, Guangdong Public Laboratory of Wild Animal Conservation and Utilization, Institute of Zoology, Guangdong Academy of Sciences, Guangzhou, Guangdong, China.; Laboratory of Genomic and Precision Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, China.; Joint Primate Research Center for Chronic Diseases, Jiangnan University and Institute of Zoology, Guangdong Academy of Sciences, Guangzhou, Guangdong, China., Xia SY; Laboratory of Genomic and Precision Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, China.; Joint Primate Research Center for Chronic Diseases, Jiangnan University and Institute of Zoology, Guangdong Academy of Sciences, Guangzhou, Guangdong, China., Hide G; Biomedical Research Centre and Ecosystems and Environment Research Centre, School of Science, Engineering and Environment, University of Salford, Salford, M5 4WT, UK., Li BH; Guangdong Key Laboratory of Animal Conservation and Resource Utilization, Guangdong Public Laboratory of Wild Animal Conservation and Utilization, Institute of Zoology, Guangdong Academy of Sciences, Guangzhou, Guangdong, China.; Joint Primate Research Center for Chronic Diseases, Jiangnan University and Institute of Zoology, Guangdong Academy of Sciences, Guangzhou, Guangdong, China., Liu YY; Guangdong Key Laboratory of Animal Conservation and Resource Utilization, Guangdong Public Laboratory of Wild Animal Conservation and Utilization, Institute of Zoology, Guangdong Academy of Sciences, Guangzhou, Guangdong, China.; Joint Primate Research Center for Chronic Diseases, Jiangnan University and Institute of Zoology, Guangdong Academy of Sciences, Guangzhou, Guangdong, China., Wei ZY; Laboratory of Genomic and Precision Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, China.; Joint Primate Research Center for Chronic Diseases, Jiangnan University and Institute of Zoology, Guangdong Academy of Sciences, Guangzhou, Guangdong, China., Zhuang XJ; Guangdong Key Laboratory of Animal Conservation and Resource Utilization, Guangdong Public Laboratory of Wild Animal Conservation and Utilization, Institute of Zoology, Guangdong Academy of Sciences, Guangzhou, Guangdong, China.; Joint Primate Research Center for Chronic Diseases, Jiangnan University and Institute of Zoology, Guangdong Academy of Sciences, Guangzhou, Guangdong, China., Yan Q; Guangdong Key Laboratory of Animal Conservation and Resource Utilization, Guangdong Public Laboratory of Wild Animal Conservation and Utilization, Institute of Zoology, Guangdong Academy of Sciences, Guangzhou, Guangdong, China.; Zhuzhou Central Hospital, Zhuzhou, Hunan, China., Wang Y; Longhua Innovation Institute for Biotechnology, Shenzhen University, Shenzhen, Guangdong, China., Yang W; Guangzhou Bay Area Institute of Biomedicine, Guangdong Lewwin Pharmaceutical Research Institute Co., Ltd., Guangdong Provincial Key Laboratory of Drug Non-Clinical Evaluation and Research, Guangzhou, Guangdong, China., Chen JH; Laboratory of Genomic and Precision Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, China. cjh_bio@hotmail.com.; Joint Primate Research Center for Chronic Diseases, Jiangnan University and Institute of Zoology, Guangdong Academy of Sciences, Guangzhou, Guangdong, China. cjh_bio@hotmail.com., Rao JH; Guangdong Key Laboratory of Animal Conservation and Resource Utilization, Guangdong Public Laboratory of Wild Animal Conservation and Utilization, Institute of Zoology, Guangdong Academy of Sciences, Guangzhou, Guangdong, China. junhuar919@163.com.; Laboratory of Genomic and Precision Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, China. junhuar919@163.com.; Joint Primate Research Center for Chronic Diseases, Jiangnan University and Institute of Zoology, Guangdong Academy of Sciences, Guangzhou, Guangdong, China. junhuar919@163.com.
Jazyk: angličtina
Zdroj: NPJ biofilms and microbiomes [NPJ Biofilms Microbiomes] 2024 Jul 26; Vol. 10 (1), pp. 61. Date of Electronic Publication: 2024 Jul 26.
DOI: 10.1038/s41522-024-00535-3
Abstrakt: 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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