Causal Relationship Between Intestinal Microbiota, Inflammatory Cytokines, Peripheral Immune Cells, Plasma Metabolome and Parkinson's Disease: A Mediation Mendelian Randomization Study

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.