Assessing causal relationships between oral microbiota and asthma: evidence from two-sample mendelian randomization analysis

Accumulating evidence indicates that alterations in the composition of the oral microbiota are associated with asthma. However, it remains uncertain whether these associations reflect causal relationships. The study aimed to investigate the causal relationship between oral microbiota and asthma at the genetic level. A two-sample Mendelian randomization (MR) analysis was conducted using genome-wide association studies (GWAS) data on the oral microbiota and asthma within the East Asian population. Inverse-variance weighted (IVW), MR-Egger, weighted median, and weighted mode methods were utilized to examine the potential causal relationship between oral microbiota and asthma. Additionally, pleiotropy and heterogeneity tests were conducted to assess the robustness of the findings. Among the 3,117 bacterial taxa analyzed, nine genera, comprising 18 oral microbiota, exhibited causal effects on asthma. Twelve oral microbiota, including Streptococcus_umgs_1936, Porphyromonas_mgs_3421, and Campylobacter_A_umgs_3382, demonstrated positive causal associations with asthma. Conversely, six oral microbiota, including Parvimonas_umgs_2046, and Parvimonas_umgs_3325, were negatively related to asthma. Enrichment was observed in three genera: Parvimonas, Streptococcus, and TM7x. No pleiotropy or heterogeneity was detected among the instrumental variables (IVs) throughout the study. The findings suggest a causal relationship between oral microbiota and asthma. These results provide novel insights into the mechanisms underlying asthma that are mediated by the oral microbiota.越来越多的证据表明，口腔微生物群（oral microbiota）组成改变与哮喘存在关联。然而，此类关联是否反映因果关系仍尚不明确。本研究旨在从遗传层面探究口腔微生物群与哮喘之间的因果关系。本研究针对东亚人群的口腔微生物群和哮喘全基因组关联研究（genome-wide association studies, GWAS）数据，开展了两样本孟德尔随机化（two-sample Mendelian randomization, MR）分析。研究采用逆方差加权（inverse-variance weighted, IVW）、MR-Egger、加权中位数（weighted median）以及加权众数（weighted mode）四种方法，对口腔微生物群与哮喘之间的潜在因果关系进行检验。此外，还通过多效性（pleiotropy）和异质性（heterogeneity）检验评估研究结果的稳健性。在分析的3117个细菌类群中，包含18个口腔微生物类群的9个菌属对哮喘存在因果效应。其中12个口腔微生物类群——包括Streptococcus_umgs_1936、Porphyromonas_mgs_3421以及Campylobacter_A_umgs_3382——与哮喘呈现正向因果关联；与之相反，包括Parvimonas_umgs_2046、Parvimonas_umgs_3325在内的6个口腔微生物类群则与哮喘呈负相关。Parvimonas、Streptococcus以及TM7x这3个菌属存在富集现象。本研究中所有工具变量（instrumental variables, IVs）均未检测到多效性或异质性。本研究结果表明口腔微生物群与哮喘之间存在因果关系。这些发现为哮喘的口腔微生物群介导发病机制提供了全新视角。