Objective Analysis of the causal relationship between intestinal flora and systemic sclerosis(SSc)using Men-delian randomization(MR).Methods We obtained genome-wide association study(GWAS)data of GI flora and SSc,screened out strong instrumental variables(instrumental variable,IV)and evaluated the causal effect by inverse-variance weighting(IVW),supplemented by MR-Egger and weighted median estimate(WME).Then,using Cochran's Q test,MR-PRESSO test,MR-Egger intercept test and leave-one-out method to evaluate robustness of results.Finally,forest plots,scat-ter plots and funnel plots related to instrumental variables were drawn.Results A total of 4 bacterial taxa were identified exhibit significant association with SSc(Collinsella genus,Ruminococcaceae UCG003 genus,Subdoligranulum genus and NB1n order)(all P<0.05).IVW:Collinsella genus(OR:7.260;95%CI:1.595-33.057),Ruminococcaceae UCG003 genus(OR:5.046;95%CI:1.463-17.400),Subdoligranulum genus(OR:0.150;95%CI:0.038-0.588);order NB1n(OR:0.389;95%CI:0.184-0.819).The results of the other two methods were consistent with IVW.Cochran Q test showed no heterogeneity,MR-PRESSO test did not find outliers,the MR-Egger intercept test showed that the results were not horizontally multivariat,and leave-one-out analysis supported robustness of the results.Conclusion The results of MR analysis supported the exist-ence of potential causal relationship between gut microbiota and SSc.Collinsella and Ruminococcaceae UCG003 genus were positively correlated with the risk of SSc,while Subdoligranulum genus and the order NB1n were negatively correlated with the risk of SSc.More research is needed to reveal how gut microbiota influences the pathogenesis of SSc.
Gut microbiotaSystemic sclerosisMendelian randomizationCausal relationshipSingle nucleotide polymor-phismInverse-variance weighting method
NETL
NSTL
万方数据
