Exploring the Causal Association Between Oral Microbiome Abundance and Asthma Risk Using Two‐Sample Mendelian Randomization

Asthma is influenced by genetic and environmental factors, and emerging evidence suggests that the oral microbiome may play a role in its pathogenesis. This study aimed to explore the causal association between oral microbiome abundance and asthma risk using a two-sample Mendelian randomization (MR) approach. We utilized genome-wide association studies (GWAS) data comprising 56,167 asthma cases and 408,442 controls of European ancestry, alongside 610 individuals from the Danish ADDITION-PRO cohort for oral microbiome analysis. We selected 267 single nucleotide polymorphisms (SNPs) linked to salivary microbiota as instrumental variables (IVs) with an F-statistic > 10. MR analyses were carried out using inverse variance weighted (IVW), MR-Egger, weighted median, and weighted mode methods, complemented by sensitivity analyses. Our findings revealed a significant association between specific salivary microbiota and asthma risk. Notably, increased abundance of Genus Rothia was positively associated with asthma risk (IVW: OR = 1.03), while an unspecified Streptococcus species showed a negative correlation (IVW: OR = 0.97). Sensitivity analyses confirmed these results' robustness, with no signs of pleiotropy or significant heterogeneity. The study suggests a causal relationship between specific oral microbiota and asthma risk, emphasizing the oral microbiome's potential significance in asthma pathogenesis.