孟德尔随机化法分析肠道菌群、血浆代谢物与上尿路结石的因果关系

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Mendelian randomization analysis of the causal relationship between gut microbiota，plasma metabolites and upper urinary tract stones

WU Guanwei， WANG Jiawei，LIU Yingqing，LIU Heqian，GAO Zehong，YAN Haifeng，GAO Xingyu， TAO Lingsong （Department of Urology，Afiliated Wuhu Hospital of East China Normal University，Wuhu 2410o，China）

ABSTRACT：ObjectiveTo explore the causal relationship between gut microbiota and upper urinary tract stones using Mendelian randomization（MR）analysis，andto investigate the potential mediatingroleof plasma metabolites.MethodsData on gutmicrobiota，plasma metabolites，and upperurinary tract stones wereobtained from publiclyavailable Genome-wide Asociation Studies（GWAS）.Bidirectional MR analysis was performed to examine thecausal relationship between gut microbiota and upper urinary tract stones.Subsequently，a two-step MR approach was employed to determine whether gut microbiota contributeto upperurinarytractstones through plasma metabolites，and themediating efects and mediatorratio werecalculated.The inversevarianceweighted（IVW）method was usedas the primaryanalytical tool，supplemented by Bayesian weighted Mendelian randomization（BWMR），MR-Eger，and weighted median（WM）analyses.Horizontal pleiotropy andheterogeneitytests wereconducted toensure therobustnesof the findings.ResultsBidirectional MRanalysis identified causalassociations between7gut microbialtaxaand6microbial metabolicpathways with upperurinarytract stones，while the developmentof upper urinarytractstones afected13gut microbialtaxaand 5 metabolic pathways.Aditionally，43plasma metabolites （including27identified metabolites，8unidentified metabolites，and8metaboliteratios）werecausallasociated with upper urinary tract stones.The two-step MR analysis identified11 potentialcausal pathways.After metabolic pathways and unidentified metabolites wereexcluded，acausallink mediatedbyBacteroidesfaecis between galactarateandupperurinarytract stones was confirmed，with a mediation proportion of 16.99% （95%CI：5.76%-33.95% P=0.037 1 ）.ConclusionThis studyestablishes acausalrelationship betweenparabacteroides andupper urinarytractstones，and elucidates the mediatingrole of galactarate，offering new insights into the pathogenesis and prevention strategies for upper urinary tract stones.

KEY WORDS：gut microbiota; plasma metabolites； upper urinary tract stones； Mendelian randomization

摘要：目的通过孟德尔随机化（MR）分析探索肠道菌群与上尿路结石之间的因果关系，并探讨血浆代谢物是否存在中介作用。（剩余13656字）