Exploring the causal relationship between acute respiratory distress syndrome and gut microbiota: Unveiling the gut-lung axis through a large-scale Mendelian randomization study

Observational studies have linked gut microbiota (GM) to acute respiratory distress syndrome (ARDS), but the cause-and-effect relationship is yet to be determined. We acquired the latest genome-wide association study (GWAS) summary statistics on GM taxa from the German (N = 8956), Dutch (N = 7738), and MibioGen (N = 18,340) consortium GWAS catalogs, as well as ARDS (Ncase = 431, Ncontrol = 4,93,301) GWAS summary statistics from the FinnGen consortium. We employed Mendelian randomization (MR) analysis using inverse-variance weighted, MR-Egger, weighted mode, and weighted median methods to investigate the causal link between GM and ARDS. We used a Bonferroni correction to account for statistical bias resulting from repeated comparisons in order to control for false positive outcomes during multiple hypothesis testing. Meta-analyses were conducted to enhance the statistical power of the MR analysis. GM had no statistically significant impact on ARDS with Bonferroni correction. Actinobacteria, Proteobacteria, Bifidobacteriales, Bifidobacteriaceae, Rikenellaceae, Dorea, Streptococcus, Bilophila wadsworthia, Escherichia unclassified, OTU99_17 (Parabacteroides), TestASV_7 (Bacteroides), TestASV_26 (Phascolarctobacterium), and TestASV_43 (Parasutterella) are notable GM taxa with low uncorrected MR inverse-variance weighted P-values, potentially indicating a reduced risk of ARDS. Bifidobacterium longum, OTU99_30 (Parasutterella), and TestASV_16 (Bacteroides) are potentially linked to an increased risk of ARDS. Meta-analyses based on 3 GWAS summary statistics suggested that Streptococcus was potentially indicating a reduced risk of ARDS (odds ratio 0.610; 95% confidence interval 0.430-0.870; P = .006). These associations were proven to be robust through analyses of sensitivity, heterogeneity, and horizontal pleiotropy. From a genetic perspective, our findings suggest a potential relationship between the GM and ARDS rather than definitive causality. Given possible confounding and methodological constraints, the results should be interpreted with caution. Additional studies are needed to elucidate underlying mechanisms and clarify microbial interactions within the GM.