Bridging the gap between gut microbiota and sleep disorders through intermediary metabolites

Research has suggested an interaction between gut microbiota and sleep, yet the causal relationships between gut microbiota, metabolites, and sleep disorders remain unclear. This study aims to uncover these relationships. We obtained genome-wide data for 196 gut microbiota species (N = 18,340), 1400 metabolites (N = 8299), and sleep disorders (N = 361,194). Mendelian randomization(MR) analyses were conducted using the Inverse Variance Weighted (IVW) method, MR-Egger, Weighted Median method, Weighted Mode method, and Simple Mode method to infer causality. The IVW method was used for primary analysis results. Significant microbiota and causal metabolites were further analyzed to clarify the associations between the three. All results were tested for heterogeneity, pleiotropy, and sensitivity to assess the stability of the findings. The Mendelian randomization results revealed causal relationships between four gut microbiota species and sleep disorders: Genus.Dorea, Genus.Parasutterell, Genus.Slackia, and Order.Bacillales. Additionally, we identified 39 causal metabolites Related to sleep disorders, with 7 of these being associated with 3 causal microbiota species at the genus level. All results showed no heterogeneity or horizontal pleiotropy. Through two-sample Mendelian randomization studies, we identified four gut microbiota species genetically linked to sleep disorders through seven plasma metabolites, revealing causal relationships between these three factors. These biomarkers provide new insights into the mechanisms of sleep disorders and may contribute to their prevention, diagnosis, and treatment.