Investigating Causal Links Between Gut Microbiota and Neurological Disorders via Genome-Wide Association Studies

Many reports have highlighted the involvement of the gut microbiome in the occurrence, progression, and outcomes of neurological disorders. However, current reports are somewhat chaotic, especially concerning whether the gut microbiota has a causal effect on various neurological diseases. Furthermore, whether there is a common mechanism involving gut microbial communities in these neurological disorders has not to be revealed. In this study, we leveraged data from the largest-scale genome-wide association study (GWAS) by the MiBioGen consortium, which includes genetic and microbial composition data from 18,340 individuals spanning 24 cohorts. We utilized single-nucleotide polymorphisms (SNPs) associated with the gut microbiome as instrumental variables (IVs) in Mendelian randomization (MR) analyses. These IVs were rigorously selected based on their genome-wide and locus-wide significance to ensure robust causal inference. Our study established robust associations between specific gut microbiota and various neurological disorders using MR. We systematically depicted the bacteria with causal relationships in all diseases, covering the levels of phylum, class, order, family, and genus. We identified 34 bacterial species as significant risk or protective factors across disorders, including two main phylum levels such as Firmicutes (22 species) and Proteobacteria (8 species), as well as Bacteroidetes (2 species), Actinobacteria (1 species), and Verrucomicrobiota (1 species). At the family level of bacteria, we found that Lachnospiraceae and Ruminococcaceae are the most related to these 11 diseases and they may play different roles in the same disease.