基于"心在窍为舌"探讨舌苔菌群和心血管疾病的因果关联:一项双样本孟德尔随机化研究OA

Objective:To systematically investigate the causal relationship between tongue-coating microbiota and cardiovascular disease(CVD),using a two-sample Mendelian randomization(MR)approach.Methods:Genetic instruments strongly associated with tongue-coating microbiota were selected(P<1×10-5,F>10)from European-descent Genome-Wide Association Study(GWAS)summary statistics of CVD(total sample:177,923;9,587,836 SNPs)and tongue-coating microbiota(n=2,017).The inverse-variance weighted(IVW)method served as the primary analysis,supplemented by sensitivity analyses(heterogeneity testing,pleiotropy assessment via MR-Egger intercept,and leave-one-out validation).Results:A total of 140,140 tongue-coating microbiota were identified to have significant associations with CVD(IVW P<0.05).Among these,increased abundance of 67 microbiota was associated with elevated CVD risk(OR range:1.01-1.04),while increased abundance of 73 microbiota demonstrated protective effects against CVD(OR range:0.97-0.99).Sensitivity analyses confirmed the robustness of these associations(MR-Egger intercept P>0.05,no evidence of reverse causality).Conclusion:This two-sample MR study provides the first genetic evidence supporting a causal link between tongue-coating microbiota and CVD,and validates the traditional Chinese medicine(TCM)theory that"the tongue is the orifice to the heart"(Xin Zai Qiao Wei She).Meanwhile,it enriches the theoretical foundation of TCM tongue diagnosis.Furthermore,this work offers novel scientific rationale for TCM strategies to targeting tongue-coating microbiota modulation to prevent and treat CVD.