口腔菌群和免疫细胞对口腔白斑病的影响:一项孟德尔随机化研究和中介分析OA

Objective To assess the causal association between specific oral microbiota and the risk of oral leuko-plakia(OLK)using a Mendelian randomization(MR)approach,and to elucidate the potential mediating role of immune cells.Methods Summary statistics from genome-wide association studies(GWAS)of the oral microbiome,GWAS data for immune cell phenotypes,and GWAS summary statistics for OLK from FinnGen were used.The inverse variance weighted(IVW)method was adopted as the primary approach,and it was supplemented by MR Egger regression,simple mode,weighted median,and weighted mode methods for additional analyses,to investigate the causal relationship be-tween 3 117 types of tongue coating and salivary microbiota,as well as 731 immune cell traits,and OLK.Furthermore,a two-step MR approach was applied to explore the potential mediating role of immune cells in the association between oral microbiota and OLK.Results IVW analysis revealed causal associations between 15 oral microbial genera and OLK.Among these,Streptococcus,Neisseria,and Catonella were associated with a reduced risk of OLK,with Fusobacte-rium showing the most significant protective effect(OR=0.41,P=0.023).In contrast,genera,including Microbacte-rium,Campylobacter,and Haemophilus_A,were linked to an increased risk of OLK,with Lancefieldella exhibiting the strongest risk effect(OR=2.66,P=0.006).Eleven immune cell phenotypes with potential causal associations with OLK were identified,including four protective and seven risk-increasing factors.Mediation analysis further identified four key mediating pathways:pathogenic genera,particularly Campylobacter_A and Lancefieldella,may promote the de-velopment and progression of OLK by upregulating highly activated pro-inflammatory immune subsets such as activated monocytes,B cells,and myeloid cells.Conversely,the potentially protective genus Catonella appeared to exert inhibi-tory effects on OLK by significantly downregulating dendritic cell subsets.Conclusion This study is the first to re-veal,at the genetic level,causal pathways through which specific oral microbial genera influence the risk of OLK by mediating immune cell responses.These findings provide novel insights into the immunopathological mechanisms un-derlying OLK and offer potential targets for intervention strategies aimed at modulating specific microbial genera or im-mune cell subsets.