Introduction:
Biomarkers of acute respiratory distress syndrome (ARDS) can provide precise treatment options. It is a clinical syndrome of diffuse lung inflammation and edema, usually leading to acute respiratory failure. We use Mendelian randomization (MR) and mediation analysis to infer the potential impact of inflammatory factors and metabolites on ARDS.

Material and methods:
The summary statistics of 1400 plasma metabolite traits and 41 inflammatory cytokine traits were obtained from publicly available GWAS. Inverse Variance Weighted were adopted for bidirectional MR analysis to infer causal relationships. Several sensitivity analyses were also used to ensure reliable MR results. Mediation analysis was used to determine the pathway from inflammatory factors to ARDS mediated by plasma metabolism and the proportion of mediation effects explained by plasma metabolites were estimated.

Results:
MR analysis revealed the causal effects of 5 inflammatory cytokines and 18 plasma metabolites on ARDS. Reverse MR analysis shows that ARDS has no effect on these 5 inflammatory cytokines. In addition, we screened 18 pathogenic metabolites associated with ARDS. Based on known pathogenic metabolites above, it was observed that through mediation analysis that Ceramide levels and Alpha tocopherol to sulfate ratio may mediate the causal pathway from inflammatory factors to ARDS, with mediation ratios of 14.1% and 17.7%, respectively (p＜0.05).

Conclusions:
The increase of Ceramide levels and Alpha-tocopherol to sulfate ratio respectively will reduce the risk of ARDS. Our research provide further insights into the complex interactions between inflammatory cytokines and metabolites in the development of ARDS, promoting the development of innovative strategies for ARDS prevention and treatment.