Systematic Mendelian randomization reveals the causal roles of the microbiome on the risk of Parkinson's disease

Abstract

Parkinsons Disease (PD) is a neurodegenerative disorder whose etiology is not fully understood. The human gut microbiome, a complex community of microorganisms residing in the digestive tract, has recently emerged as a potential factor influencing various health conditions, including neurodegenerative diseases. The causal involvement of the human gut microbiome in Parkinsons disease (PD) remains elusive, primarily due to the challenge of distinguishing causation from mere correlation, and the presence of contradictory findings in existing research. The relationship between the gut microbiome and PD was assessed using a two-sample Mendelian randomization (MR) approach. Assessing the impact of microbial traits using data from independent genome-wide association studies (GWAS) (comprising 2,259 samples) on PD within a cohort of 15,056 cases and 449,056 controls. We performed multiple sensitivity analyses to validate our findings. Preliminary MR analysis indicated that modifications in the bacterial composition of the Firmicutes and Proteobacteria phyla are associated with changes in PD risk. Additionally, bacteria in other genera also play a role in this causal association. We provide a comprehensive discussion of the results obtained from our MR analysis and highlight the distinctions between our study and prior research efforts.