Causal effects of gut microbiota on ARDS: a two-sample Mendelian randomization study

Abstract

Abstract Background A growing number of studies showed that altered gut microbiota is associated with the pathogenesis of ARDS. However, the potential causal relationship remained unclear. Herein, we adopted a two-sample Mendelian randomization (MR) study to investigate the causal relationship between gut microbiota and ARDS. Methods We used publicly available genome-wide association study (GWAS) summary data to perform MR analysis. Gut microbiota GWAS were obtained from the MiBioGen study and summary-level GWAS dataset for ARDS were obtained from the IEU OpenGWAS Project. MR-Egger, weighted median, inverse variance weighted (IVW), simple mode and weighted mode methods were used to investigate the causal relationship and IVW method was considered as the primary approach. Additionally, a set of sensitivity analyses, including the MR-Egger intercept test, Cochran’s Q test, and leave-one-out test, were carried out to evaluate the robustness of our findings. Results Our study identified eight microbial taxa that were causally associated with ARDS risk. The increased abundance of Phylum Actinobacteria(odds ratio [OR]: 0.22, 95% confidence interval [CI]:0.07-0.68, P=0.008), genus Intestinibacter(OR: 0.40, 95% CI: 0.16–0.98, P=0.045) and genus Eubacterium ruminantium group (OR: 0.52, 95% CI: 0.27–1.00, P=0.049) were negatively associated with the risk of ARDS, while the abundance of genus Victivallis (OR: 2.55, 95% CI: 1.22–5.35, P=0.013), class Erysipelotrichia(OR:3.69 , 95% CI: 1.06-12.82, P=0.040), order Erysipelotrichales(OR:3.69, 95%CI:1.06-12.82,P=0.040), family Erysipelotrichaceae(OR: 3.69, 95% CI: 1.06-12.82, P=0.040), and genus Ruminococcaceae UCG014 (OR:2.92, 95% CI: 1.02-8.34, P=0.044) were positively correlated with the risk of ARDS. Sensitivity analysis revealed no evidence of heterogeneity and pleiotropy. Conclusions This study is the first to provide suggestive evidence for a causal relationship between certain gut microbiota and the risk of ARDS, providing valuable insights into the pathogenesis of microbiota-mediated ARDS and potential targets for ARDS treatment.