Causal relationship between gut microbiome, immune cell, and systemic lupus erythematosus: A Mendelian randomization analysis

Systemic lupus erythematosus (SLE) is a highly heterogeneous, multifactorial complex disease. Its pathogenic mechanisms are extremely intricate, primarily characterized by immune dysregulation caused by the combined influence of genetic, environmental, and biological factors. In recent years, increasing evidence has shown that gut microbiome play a crucial role in the onset and progression of SLE. However, no study has yet specifically elucidated the mechanisms by which gut microbiome influence SLE. Based on the central role of immune cells in immune balance and the pathogenesis of SLE, we propose the hypothesis that gut microbiome affect the onset and progression of SLE through the regulation of immune cells. To test this hypothesis, we utilized large-scale genome-wide association studies data from a cohort of gut microbiome, 713 immune cell types, and SLE patients. We conducted large-scale Mendelian randomization and mediation analyses to explore the causal relationships between gut microbiota, immune cells, and SLE. The results indicate that immune cells mediate the causal relationship between gut microbiome and SLE, and 2 specific upstream and downstream regulatory mechanisms were identified. These findings provide new insights and a theoretical foundation for the development of therapeutic targets for SLE.