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Published on: July 31, 2019
Causal Relationship Between Intestinal Microbiota, Inflammatory Cytokines, Peripheral Immune Cells, Plasma Metabolome
Chengcheng Wang1, Yuhang Tang1, Tao Yang1
1Department of Neurosurgery, Affiliated Chuzhou Hospital of Anhui Medical University, First People's Hospital of Chuzhou, Chuzhou, China.
Abstract:
Parkinson's disease (PD) is a neurodegenerative disease involving multiple factors. We explored the connection between intestinal microbiome levels and PD by examining inflammatory cytokines, peripheral immune cell counts and plasma metabolomics as potential factors. By obtaining the Genome-Wide Association Study (GWAS) data needed for this study from GWAS Catalog, including summary data for 473 intestinal microbiota traits (N = 5959), 91 inflammatory cytokine traits (N = 14,824), 118 peripheral immune cell count traits (N = 3757), 1400 plasma metabolite traits (N = 8299) and PD traits (N = 482,730). We used two-step Mendelian randomization (MR) mediated analysis to investigate possible pathways from intestinal microbiota to PD mediated by inflammatory cytokines, peripheral immune cells and plasma metabolites. MR has revealed the causal effects of 19 intestinal microbiota, 1 inflammatory cytokine and 12 plasma metabolites on PD, whereas there is no significant causal relationship between immune cell count characteristics and the occurrence of PD. Mediation analysis showed that the associations between the genus Demequina and PD were mediated by tryptophan with mediated proportions of 17.51% (p = 0.0393). Our study demonstrates that genus Demequina may promote the occurrence of PD by reducing the levels of tryptophan.
Insights
The gut bacterium genus Demequina may increase Parkinson's disease (PD) risk by lowering tryptophan levels. This study used Mendelian randomization to explore gut microbiome links to PD.
Area of Science:
- Neuroscience
- Genetics
- Microbiology
Background:
- Parkinson's disease (PD) is a complex neurodegenerative disorder with multifactorial causes.
- The gut microbiome's role in PD pathogenesis is increasingly recognized.
- Investigating the interplay between gut microbiota, immune responses, and metabolic pathways is crucial for understanding PD.
Purpose of the Study:
- To explore the causal relationships between intestinal microbiota, inflammatory cytokines, peripheral immune cells, plasma metabolites, and Parkinson's disease.
- To identify potential mediating factors in the pathway from gut microbiota to PD.
- To elucidate the specific role of the gut bacterium genus Demequina in PD development.
Main Methods:
- Utilized two-step Mendelian randomization (MR) analysis.
- Employed Genome-Wide Association Study (GWAS) summary data for multiple traits including intestinal microbiota, inflammatory cytokines, immune cells, plasma metabolites, and PD.
- Performed mediation analysis to assess the role of specific metabolites in the microbiota-PD association.
Main Results:
- Identified causal effects of 19 intestinal microbiota, 1 inflammatory cytokine, and 12 plasma metabolites on PD risk.
- Found no significant causal link between peripheral immune cell counts and PD.
- Demonstrated that the association between genus Demequina and PD is mediated by reduced tryptophan levels (17.51% mediation).
Conclusions:
- Genus Demequina may contribute to Parkinson's disease development by decreasing tryptophan levels.
- This study highlights specific gut microbiota and metabolic pathways as potential therapeutic targets for PD.
- The findings underscore the gut-brain axis's importance in neurodegenerative diseases like PD.
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