Exploring the mediating role of plasma lipidome in the pathway from gut microbiota to dementia: A Mendelian randomization study

Introduction Previous studies have indicated a possible connection between Gut microbiota (GM) and dementia, however, the exact cause-and-effect relationships between GM, various types of dementia, and the potential influence of plasma lipidome as intermediaries are still unclear. Material and methods We used genome-wide association study (GWAS) data to identify GM, plasma lipidome, and five types of dementia, including Alzheimer’s disease (AD), dementia with Lewy bodies (DLB), Parkinson's disease dementia (PDD), frontotemporal dementia (FTD) and vascular dementia (VD). We used Mendelian randomization (MR) to investigate the possible causal connections among GM, plasma lipidome, and dementias. The inverse variance weighting (IVW) method served as the primary statistical approach. We investigated the role of plasma lipidome as a potential mediating factor in this relationship. Results A total of 41 positive and 39 negative causal relationships between genetic susceptibility in the GMs or bacterial pathway and dementia, as well as 14 negative causal relationships between plasma lipidome and dementias. Additionally, only 1 potential mediation pathway was identified as having a significant mediating effect. Conclusions Our results suggest a link between GM and plasma lipidome with five distinct types of dementia, indicating that Phosphatidylcholine (O-16:1_18:2) level could play a role in the pathway from species Bacteroides coprocola to vascular dementia.