Gut microbiota and childhood asthma: A 2-sample bidirectional Mendelian randomization study

The causal relationship linking the human gut microbiota to childhood asthma remains inadequately defined. A bidirectional, 2-sample Mendelian randomization (MR) analysis was therefore conducted to investigate this potential causal association. Utilizing publicly accessible genome-wide association study summary data, we applied 2-sample MR to infer causality. The primary causal effect estimates were generated through inverse variance weighted meta-analysis. Sensitivity analyses included the weighted median, MR-Egger, and MR pleiotropy residual sum and outlier approaches. Robustness and evidence for pleiotropy were assessed using Cochran Q test, the MR-Egger intercept test, and leave-one-out sensitivity analysis. To investigate potential reverse causation, we performed a reverse MR analysis. MR analysis suggested a potential causal relationship between gut microbiota and childhood asthma. Using the inverse variance weighted method, it was found that genetically predicted class.Coriobacteriia (OR = 0.807; 95% confidence interval [CI]: 0.661-0.986; P = .036), family. Coriobacteriaceae (OR = 0.807; 95% CI: 0.661-0.986; P = .036), genus. Bilophila (OR = 0.825; 95% CI: 0.684-0.995; P = .044) and order. Enterobacteriales (OR = 0.807; 95% CI: 0.661-0.986; P = .036) were inversely associated with the risk of childhood asthma, while the association between genetically predicted genus. Catenibacterium (OR = 1.201; 95% CI: 1.017-1.418; P = .031) and childhood asthma was positive. The reverse MR analysis revealed that genus. Blautia (OR = 0.953; 95% CI: 0.910-0.999; P = .046), genus. Marvinbryantia (OR = 0.930; 95% CI: 0.881-0.981; P = .008), genus. Ruminococcus1 (OR = 0.951; 95% CI: 0.908-0.996; P = .032), genus.Tyzzerella3 (OR = 0.896; 95% CI: 0.808-0.994; P = .039) and phylum. Lentisphaerae (OR = 0.917; 95% CI: 0.841-1.000; P = .049) were significantly negatively correlated with childhood asthma. Evidence from this study confirms a causal role of gut microbial communities in childhood asthma etiology. This insight paves the way for microbiota-directed prevention frameworks and biomarker-driven asthma diagnostics in children.