Casual roles of gut microbiota, immune cells, and inflammatory cytokines in acute respiratory distress syndrome: a two-sample Mendelian randomization study and mediation analysis

Abstract

The complex interaction between the gut microbiome and the host’s immune system is pivotal in the development of acute respiratory distress syndrome (ARDS). Despite this, the relationship between gut microbiota, inflammation, and ARDS has not been fully investigated. In this study, we conducted a genome-wide association study (GWAS) employing summary statistics related to gut microbiota, immune cells, circulating inflammatory cytokines, and outcomes of ARDS. Our primary analytical strategy incorporated five methodologies, predominantly utilizing the Inverse-Variance Weighted (IVW) approach within the framework of MR. Heterogeneity was assessed using Cochran’s Q test, while horizontal pleiotropy was evaluated through MR-Egger regression. Additionally, sensitivity analyses and reverse MR were performed to ensure the robustness of the findings. Following adjustments for the false discovery rate (FDR), our findings indicated that, although the overall effects of exposures on ARDS were not statistically significant, there were causal associations identified for 12 gut microbiota taxa, 25 immune cells, and 6 circulating inflammatory cytokines with ARDS (p < 0.05). Mediation analysis revealed that cytokines Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1), caspase 8, IL-6, and IL-8 served as partial mediators in the influence exerted by gut microbiota. These findings confirm the potential associations between gut microbiota, immunophenotypes, and inflammatory cytokines with ARDS, shedding light on the mechanisms through which these factors may contribute to the condition and providing a foundation for future investigations into targeted prevention strategies.